Neoantigens in Chronic Obstructive Pulmonary Disease and Lung Cancer: A Point of View. Zeneyedpour Lona,Dekker Lennard J M,van Sten-van T Hoff Jenny J M,Burgers Peter C,Ten Hacken Nick H T,Luider Theo M Proteomics. Clinical applications The goal of this manuscript is to explore the role of clinical proteomics for detecting mutations in chronic obstructive pulmonary disease (COPD) and lung cancer by mass spectrometry-based technology. COPD and lung cancer caused by smoke inhalation are most likely linked by challenging the immune system via partly shared pathways. Genome-wide association studies have identified several single nucleotide polymorphisms which predispose an increased susceptibility to COPD and lung cancer. In lung cancer, this leads to coding mutations in the affected tissues, development of neoantigens, and different functionality and abundance of proteins in specific pathways. If a similar reasoning can also be applied in COPD will be discussed. The technology of mass spectrometry has developed into an advanced technology for proteome research detecting mutated peptides or proteins and finding relevant molecular mechanisms that will enable predicting the response to immunotherapy in COPD and lung cancer patients. 10.1002/prca.201800093
    The potential impact of chronic obstructive pulmonary disease in lung cancer screening: implications for the screening clinic. Young Robert P,Hopkins Raewyn Expert review of respiratory medicine : Following the findings of the National Lung Screening Trial (NLST), lung cancer screening is now recommended in the United States. However, post-hoc analyses of the NLST suggest that reducing lung cancer mortality through screening is highly dependent on the underlying characteristics of the screening participants, in particular, the presence of chronic obstructive pulmonary disease (COPD). : In this review, we outline how outcomes in lung cancer screening are significantly affected by the presence of airflow limitation, as caused by COPD, and how this might impact the assessment of eligible smokers in a lung cancer screening clinic. : There is growing evidence showing that CT-based screening for lung cancer reduces lung cancer mortality. The benefits of screening exceed those seen in the NLST when screening is carried out in lower risk populations, for a longer duration, and when outcomes are compared with usual care control cohorts. In this article, we review data from a post-hoc analysis of the NLST. We suggest that whilst worsened airflow limitation is associated with greater lung cancer risk, there is also more aggressive lung cancer, reduced lung cancer operability, and for advanced COPD, reduced benefits from screening. We advocate an 'outcomes-based' approach to screening over a 'risk-based' approach. 10.1080/17476348.2019.1638766
    PIK3CA mutation as a distinctive genetic feature of non-small cell lung cancer with chronic obstructive pulmonary disease: A comprehensive mutational analysis from a multi-institutional cohort. Sawa Kenji,Koh Yasuhiro,Kawaguchi Tomoya,Kambayashi Satoshi,Asai Kazuhisa,Mitsuoka Shigeki,Kimura Tatsuo,Yoshimura Naruo,Yoshimoto Naoki,Kubo Akihito,Saka Hideo,Matsumura Akihide,Wanibuchi Hideki,Yamamoto Nobuyuki,Nishiyama Noritoshi,Hirata Kazuto Lung cancer (Amsterdam, Netherlands) OBJECTIVES:Non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) have been proposed to have a mutual developmental mechanism, but their association has not been fully understood. We aimed to examine the association of the mutational landscape of NSCLC with co-morbid COPD. MATERIALS AND METHODS:A total of 197 surgical specimens of early stage NSCLC were retrospectively collected from two independent sources, namely, the Japan Molecular Epidemiology for Lung Cancer Study and the Osaka City University Hospital cohort from 2010 to 2013. COPD and its severity were defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and grading system. For molecular profiling of NSCLC patients with COPD, the extracted DNAs were deep-sequenced using next generation sequence technologies for somatic mutations in a maximum 72 cancer-associated genes. Logistic regression analysis was performed to evaluate the impact of COPD on the somatic mutations. RESULTS:The COPD group (n=77), including 56 GOLD 1 and 21 GOLD 2 or 3 patients, had 58 squamous cell lung carcinoma (SCC) cases and 19 adenocarcinoma cases. The non-COPD group (n=120) had 53 SCC cases, 64 adenocarcinoma cases, and three cases with other histology. The frequency of PIK3CA mutation was significantly higher in the COPD group than in the non-COPD group (10.4% vs. 1.7%, p=0.015). Meanwhile, NFE2L2 mutation was observed only in SCC cases, with no difference in the frequency between the two groups (17.2% vs. 17.0%). In the multivariate logistic regression model with consideration for COPD status, age, smoking dose, pathological stage, and histology, significantly more PIK3CA mutation was observed in the presence of COPD (odds ratio=5.31, 95% CI: 1.03-27.29, p=0.046). CONCLUSIONS:PIK3CA mutation is a distinctive genetic feature of NSCLC with COPD, regardless of age, smoking dose, pathological stage, and histology. 10.1016/j.lungcan.2017.07.039
    Protein phosphatase 2A (PP2A): a key phosphatase in the progression of chronic obstructive pulmonary disease (COPD) to lung cancer. Nader Cassandra P,Cidem Aylin,Verrills Nicole M,Ammit Alaina J Respiratory research Lung cancer (LC) has the highest relative risk of development as a comorbidity of chronic obstructive pulmonary disease (COPD). The molecular mechanisms that mediate chronic inflammation and lung function impairment in COPD have been identified in LC. This suggests the two diseases are more linked than once thought. Emerging data in relation to a key phosphatase, protein phosphatase 2A (PP2A), and its regulatory role in inflammatory and tumour suppression in both disease settings suggests that it may be critical in the progression of COPD to LC. In this review, we uncover the importance of the functional and active PP2A holoenzyme in the context of both diseases. We describe PP2A inactivation via direct and indirect means and explore the actions of two key PP2A endogenous inhibitors, cancerous inhibitor of PP2A (CIP2A) and inhibitor 2 of PP2A (SET), and the role they play in COPD and LC. We explain how dysregulation of PP2A in COPD creates a favourable inflammatory micro-environment and promotes the initiation and progression of tumour pathogenesis. Finally, we highlight PP2A as a druggable target in the treatment of COPD and LC and demonstrate the potential of PP2A re-activation as a strategy to halt COPD disease progression to LC. Although further studies are required to elucidate if PP2A activity in COPD is a causal link for LC progression, studies focused on the potential of PP2A reactivating agents to reduce the risk of LC formation in COPD patients will be pivotal in improving clinical outcomes for both COPD and LC patients in the future. 10.1186/s12931-019-1192-x
    Static lung hyperinflation is an independent risk factor for lung cancer in patients with chronic obstructive pulmonary disease. Zamarrón Ester,Prats Eva,Tejero Elena,Pardo Paloma,Galera Raúl,Casitas Raquel,Martínez-Cerón Elisabet,Romera Delia,Jaureguizar Ana,García-Río Francisco Lung cancer (Amsterdam, Netherlands) INTRODUCTION:Static hyperinflation, a hallmark characteristic of some patients with chronic obstructive pulmonary disease, is related to higher mortality and cardiovascular morbidity. However, information about its association with lung cancer is scarce. Our aim was to evaluate whether static hyperinflation is associated with future risk of lung cancer in COPD patients. METHODS:A cohort of 848 COPD patients recruited outside the hospital setting was monitored for an average period of 4.3 years, totaling 2858 person-years, regarding diagnosis of cancer of any origin or lung cancer. Static hyperinflation was defined by functional residual capacity measured by plethysmography greater than 120% of the predicted value. RESULTS:The incidence rates for cancer of any origin and lung cancer were 16.0 (95%CI, 15.1-17.8) and 8.7 (95%CI, 7.7-9.8) per 1000 patient-years, respectively. Among the patients with lung cancer, non-small cell lung cancer predominated (88%). In a stepwise multivariate Cox regression model, body mass index (BMI), pack-years, Charlson index, and postbronchodilator FEV/FVC ratio were retained as independent predictors of cancer of any origin. In contrast, features associated with a future risk of lung cancer included older age, low BMI, increased pack-years and presence of static hyperinflation (adjusted hazard ratio: 4.617, 95%CI: 1.007-21.172, p = 0.049). CONCLUSION:In a general COPD outpatient population, static hyperinflation is an independent risk factor for the development of lung cancer, which might contribute towards justifying the excess mortality identified in COPD patients with hyperinflation. 10.1016/j.lungcan.2018.12.012
    [Clinical Characteristics of 118 Cases of Chronic Obstructive Pulmonary Disease Complicated with Primary Bronchopulmonary Carcinoma]. Zhao Songlin,Nie Xiuhong,Zhang Lin,Zhang Wei,Xiao Han Zhongguo fei ai za zhi = Chinese journal of lung cancer BACKGROUND:The aim of this study is to investigate the clinical characteristics of patients with primary bronchopulmonary carcinoma complicated with chronic obstructive pulmonary disease (COPD), and to optimize the early diagnoses in the coexistence of COPD and primary bronchopulmonary carcinoma. METHODS:The clinical data of 118 patients with COPD complicated with primary bronchopulmonary carcinoma were analyzed retrospectively, including age, sex, smoking history, smoking index, clinical symptoms and signs, pathological type, staging, metastasis site and lung function index. 120 patients with simple COPD were selected as control. RESULTS:The smoking rate (55.1%) and smoking index ≥400 branch /year (90.8%) of the patients with COPD complicated with primary bronchopulmonary carcinoma were higher than the simple COPD group (20.8%, 48.0%). The difference between the two groups was statistically significant (P<0.01). There were no significant differences in the incidence of common symptoms such as cough, sputum, fever, fatigue and dyspnea in COPD complicated with primary bronchopulmonary carcinoma patients with simple COPD group (P>0.05), while the incidence of hemoptysis, weight loss, chest pain, hoarseness, pleural effusion and atelectasis were significantly higher than those in simple COPD group (P<0.01). When the patients were first diagnosed as COPD with primary bronchopulmonary carcinoma, 63.6% of the group were advanced or located late, and the distant metastases are common for pleural metastasis and bone metastases. There was no significant difference in forced expiratory volume in one second/forced vital capacity (FEV1/FVC), FEV1% pre, total lung capacity (TLC) and residual volume (RV)/TLC between the two groups (P>0.05), but the diffusing capacity of carbon monoxide (DLCO) of COPD patients complicated with primary bronchopulmonary carcinoma was lower than that of simple COPD patients (P<0.05) . In the COPD patients with primary bronchopulmonary carcinoma, squamous cell carcinoma was the most common pathological type (51.7%). Male patients were mainly squamous cell carcinoma (60.7%), while female patients with adenocarcinoma (69.0%). CONCLUSIONS:COPD combined with primary bronchopulmonary carcinoma occurs in male smokers more. There is higher incidence of squamous cell carcinoma. When they are first diagnosed, most of them are advanced or located late, due to no specific clinical symptoms at the early stages. Periodic chest CT examination for COPD patients can help early diagnoses of primary bronchopulmonary carcinoma.
. 10.3779/j.issn.1009-3419.2017.08.07
    [Impact of Chronic Obstructive Pulmonary Disease on Risk of Recurrence in Patients with Resected Non-small Cell Lung Cancer]. Qiang Guangliang,Yu Qiduo,Liang Chaoyang,Song Zhiyi,Shi Bin,Guo Yongqing,Liu Deruo Zhongguo fei ai za zhi = Chinese journal of lung cancer BACKGROUND:Lung cancer and chronic obstructive pulmonary disease (COPD) are both common diseases in respiratory system and the leading causes of deaths worldwide. The purpose of this study was to determine whether the severity of COPD affects long-term survival in non-small cell lung cancer (NSCLC) patients after surgical resection. METHODS:A retrospective research was performed on 421 consecutive patients who had undergone lobectomy for NSCLC. Classification of COPD severity was based on guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Characteristics among the three subgroups were compared and recurrence-free survivals were analyzed. RESULTS:A total of 172 patients were diagnosed with COPD, 124 as mild (GOLD-1), 46 as moderate(GOLD-2), and 2 as severe (GOLD-3). The frequencies of recurrence were significantly higher in higher COPD grades group (P<0.001). Recurrence-free survival at five years were 78.1%, 70.4%, and 46.4% in Non-COPD, GOLD-1 COPD, and GOLD-2/3 COPD groups, respectively (P<0.001). In univariate analysis, age, gender, smoking history, COPD severity, tumor size, histology and pathological stage were associated with recurrence-free survival. Multivariate analyses showed that older age, male, GOLD-2/3 COPD, and advanced stage were independent risk factors associated with recurrence-free survival. CONCLUSIONS:NSCLC patients with COPD are at higher risk for postoperative recurrence, and moderate/severe COPD is an independent unfavorable prognostic factor. The severity of COPD based on pulmonary function test can be a useful indicator to identify patients at high risk for recurrence. Therefore, it can contribute to adequate selection of the appropriate individualized treatment. 10.3779/j.issn.1009-3419.2018.03.21
    Comparison of clinical characteristics and overall survival between spirometrically diagnosed chronic obstructive pulmonary disease (COPD) and non-COPD never-smoking stage I-IV non-small cell lung cancer patients. Lim Jeong Uk,Yeo Chang Dong,Rhee Chin Kook,Kang Hye Seon,Park Chan Kwon,Kim Ju Sang,Kim Jin Woo,Kim Seung Joon,Yoon Hyoung Kyu,Lee Sang Haak International journal of chronic obstructive pulmonary disease A significant proportion of non-small cell lung cancer (NSCLC) patients are never-smokers. However, the clinical impact of spirometrically diagnosed chronic obstructive pulmonary disease (COPD) on the prognosis of never-smoking NSCLC has not been evaluated in the context of treatment modalities and other cancer-related factors. In the present study, we evaluated the clinical impact of COPD in non-smoking NSCLC patients, and correlations between COPD and other previously unevaluated clinical variables. Lung cancer patients (stages I to IV) diagnosed with NSCLC between January 2008 and December 2015 at six university hospitals were enrolled in the study cohort and retrospectively evaluated. Clinical parameters were compared between spirometrically diagnosed COPD and non-COPD groups. Correlations between COPD status and other variables were evaluated. In order to reduce the effect of potential confounders and selection bias, we performed adjustment for differences in baseline parameters by using propensity score matching (PSM). After PSM, clinical variables were evaluated for their effects on overall survival (OS). Of the 345 patients enrolled in the study, 277 were categorized as non-COPD and 68 as COPD. Old age, male gender, and wild-type EGFR were significantly correlated with COPD. By univariate analysis of 218 patients in a propensity score matched cohort, not receiving active anticancer treatment, advanced stage, and COPD were significantly associated with shorter OS. Multivariate analysis showed that not receiving active anticancer treatment, advanced cancer stage, and COPD (=0.044, HR: 1.526, 95% CI: 1.012-2.300) were significant predictors of shorter OS. In the present study, never-smoker NSCLC patients with COPD had shorter OS times, compared to non-COPD never-smoker NSCLC patients. 10.2147/COPD.S190244
    Impact of chronic obstructive pulmonary disease on the mortality of patients with non-small-cell lung cancer. Lee Seung Jun,Lee Jinwoo,Park Young Sik,Lee Chang-Hoon,Lee Sang-Min,Yim Jae-Joon,Yoo Chul-Gyu,Han Sung Koo,Kim Young Whan Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer INTRODUCTION:The impact of chronic obstructive pulmonary disease (COPD) on the mortality of patients with lung cancer has not been studied extensively. The objective of this study is to compare the mortality and clinical characteristics of patients with non-small-cell lung cancer (NSCLC) according to the presence of COPD. METHODS:The medical records of 221 smokers diagnosed with NSCLC were reviewed. Eligible patients were dichotomized into the COPD group (n = 111) and the non-COPD group (n = 110). The overall survival and clinical characteristics were compared, and predictors of worse survival were analyzed using Cox proportional hazards regression. RESULTS:COPD was present in 50.2% of all patients with NSCLC, and most of the patients (92.8%) with COPD were unaware of the disease before the diagnosis of lung cancer. Patients in the COPD group were older and had a lower body mass index, higher pack-years smoking history, higher frequency of dyspnea, and higher incidence of previous malignancy. The overall survival of enrolled patients and propensity score-matched subjects was comparable between the two groups (log-rank test, p = 0.2 and 0.396, respectively). Old age, low body mass index, advanced disease stage (stages III and IV), non-squamous histology, Eastern Cooperative Oncology Group performance status of greater than or equal to 2, weight loss, and coexistence of interstitial lung disease were independent risk factors for shorter survival. CONCLUSION:COPD frequently and subliminally coexists with NSCLC. Although differences in clinical characteristic did exist, there was no impact of COPD on the mortality of patients with NSCLC with a positive smoking history in this study. 10.1097/JTO.0000000000000158
    Effect of COPD on symptoms, quality of life and prognosis in patients with advanced non-small cell lung cancer. Yi Young-Soo,Ban Woo Ho,Sohng Kyeong-Yae BMC cancer BACKGROUND:Many studies have reported the prevalence of chronic obstructive pulmonary disease (COPD) and its effects and prognosis in patients with lung cancer, but few have considered quality of life and survival of patients with lung cancer according to severity of airway obstruction. This study investigated the presence of COPD and the severity of airway obstruction in patients with non-small cell lung cancer (NSCLC), and analyzed how these factors affected symptoms, quality of life, and prognosis. METHODS:We retrospectively reviewed the prospective lung cancer database of the Catholic Medical Centers at the Catholic University of Korea from 2014 to 2017. We enrolled patients with advanced NSCLC and evaluated quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30. We also estimated pulmonary function and analyzed survival data. RESULTS:Of the 337 patients with advanced NSCLC, 170 (50.5%) had COPD and 167 (49.5%) did not. Significant differences were observed in symptoms between the two groups. The COPD group complained of more symptoms, such as cough, sputum, and dyspnea, than those in the non-COPD group. The distribution according to the severity of obstruction in the COPD group was as follows: Grade 1 (FEV ≥ 80%) 35 patients (20.6%), Grade 2 (50% ≤ FEV < 80%) 103 patients (60.6%), Grade 3 (30% ≤ FEV < 50%) 24 patients (14.1%), and Grade 4 (FEV < 30%) 8 patients (4.7%). The presence of COPD did not affect overall quality of life in patients with NSCLC, but as the airway obstruction increased, physical function decreased, and fatigue and dyspnea were more frequent. The overall median survival of the COPD group was shorter than that of the non-COPD group (median survival, 224 vs. 339 days, p = 0.035). CONCLUSIONS:In this study, a high prevalence of COPD was found among patients with advanced NSCLC, and COPD patients complained about various symptoms and had diminished quality of life in several sectors. Therefore, it is necessary to actively evaluate quality of life, lung function, and symptoms in patients with lung cancer and reflect them in the treatment and management plans of these patients. 10.1186/s12885-018-4976-3
    Metabolomics provide new insights on lung cancer staging and discrimination from chronic obstructive pulmonary disease. Deja Stanislaw,Porebska Irena,Kowal Aneta,Zabek Adam,Barg Wojciech,Pawelczyk Konrad,Stanimirova Ivana,Daszykowski Michal,Korzeniewska Anna,Jankowska Renata,Mlynarz Piotr Journal of pharmaceutical and biomedical analysis Chronic obstructive pulmonary disease (COPD) and lung cancer are widespread lung diseases. Cigarette smoking is a high risk factor for both the diseases. COPD may increase the risk of developing lung cancer. Thus, it is crucial to be able to distinguish between these two pathological states, especially considering the early stages of lung cancer. Novel diagnostic and monitoring tools are required to properly determine lung cancer progression because this information directly impacts the type of the treatment prescribed. In this study, serum samples collected from 22 COPD and 77 lung cancer (TNM stages I, II, III, and IV) patients were analyzed. Then, a collection of NMR metabolic fingerprints was modeled using discriminant orthogonal partial least squares regression (OPLS-DA) and further interpreted by univariate statistics. The constructed discriminant models helped to successfully distinguish between the metabolic fingerprints of COPD and lung cancer patients (AUC training=0.972, AUC test=0.993), COPD and early lung cancer patients (AUC training=1.000, AUC test=1.000), and COPD and advanced lung cancer patients (AUC training=0.983, AUC test=1.000). Decreased acetate, citrate, and methanol levels together with the increased N-acetylated glycoproteins, leucine, lysine, mannose, choline, and lipid (CH3-(CH2)n-) levels were observed in all lung cancer patients compared with the COPD group. The evaluation of lung cancer progression was also successful using OPLS-DA (AUC training=0.811, AUC test=0.904). Based on the results, the following metabolite biomarkers may prove useful in distinguishing lung cancer states: isoleucine, acetoacetate, and creatine as well as the two NMR signals of N-acetylated glycoproteins and glycerol. 10.1016/j.jpba.2014.08.020
    Impact of chronic obstructive pulmonary disease on postoperative recurrence in patients with resected non-small-cell lung cancer. Qiang Guangliang,Liang Chaoyang,Xiao Fei,Yu Qiduo,Wen Huanshun,Song Zhiyi,Tian Yanchu,Shi Bin,Guo Yongqing,Liu Deruo International journal of chronic obstructive pulmonary disease PURPOSE:This study aimed to determine whether the severity of chronic obstructive pulmonary disease (COPD) affects recurrence-free survival in non-small-cell lung cancer (NSCLC) patients after surgical resection. PATIENTS AND METHODS:A retrospective study was performed on 421 consecutive patients who had undergone lobectomy for NSCLC from January 2008 to June 2011. Classification of COPD severity was based on guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Characteristics among the three subgroups were compared and recurrence-free survivals were analyzed. RESULTS:A total of 172 patients were diagnosed with COPD (124 as GOLD-1, 46 as GOLD-2, and two as GOLD-3). The frequencies of recurrence were significantly higher in patients with higher COPD grades (P<0.001). Recurrence-free survival at 5 years was 78.1%, 70.4%, and 46.4% in non-COPD, mild COPD, and moderate/severe COPD groups, respectively (P<0.001). By univariate analysis, the age, sex, smoking history, COPD severity, tumor size, histology, and pathological stage were associated with recurrence-free survival. Multivariate analysis showed that older age, male, moderate/severe COPD, and advanced stage were independent risk factors associated with recurrence-free survival. CONCLUSION:NSCLC patients with COPD are at high risk for postoperative recurrence, and moderate/severe COPD is an independent unfavorable prognostic factor. 10.2147/COPD.S97411
    Improved treatment outcome of pembrolizumab in patients with nonsmall cell lung cancer and chronic obstructive pulmonary disease. Shin Sun Hye,Park Hye Yun,Im Yunjoo,Jung Hyun Ae,Sun Jong-Mu,Ahn Jin Seok,Ahn Myung-Ju,Park Keunchil,Lee Ho Yun,Lee Se-Hoon International journal of cancer Emerging immune profiling data suggest a higher sensitivity to immune checkpoint inhibitors (ICIs) in nonsmall cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD), compared to those without COPD. This study aimed to investigate the clinical impact of COPD on the treatment response to ICIs in a large number of patients with NSCLC. In total, 133 patients with spirometry test results were retrospectively identified among those who received palliative pembrolizumab for NSCLC. COPD was defined as pre-bronchodilator forced expiratory volume in 1 s/forced vital capacity <0.7. Overall survival (OS), progression-free survival (PFS), and objective response rate were analyzed according to the presence of COPD. Spirometry-based COPD was present in 59 (44%) patients. Patients with COPD had better OS (hazard ratio [HR] for death, 0.45; 95% confidence interval [CI], 0.26-0.78) and PFS (HR for disease progression or death, 0.50; 95% CI, 0.31-0.79) than those without COPD. These associations persisted after adjusting for potential confounders including smoking history. The response rate was also higher in patients with COPD than in those without COPD (38.2% vs. 20.5%, p = 0.028). Spirometry-defined COPD was associated with a significantly longer OS and PFS in patients with NSCLC treated with palliative pembrolizumab. Identifying coexisting COPD could predict favorable treatment outcomes in patients with NSCLC treated with pembrolizumab. 10.1002/ijc.32235
    and are chronic obstructive pulmonary disease-related genes that facilitate squamous cell lung cancer progression. Wang Lijing,Zhao Hongjun,Zhang Lemeng,Luo Hui,Chen Qiong,Zuo Xiaoxia Oncology letters Chronic obstructive pulmonary disease (COPD) and squamous cell lung carcinoma (SCC) are smoking-related diseases. However, the connection between the two is poorly understood. Microarray gene expression profiles in bronchial epithelium from patients with SCC with or without COPD were downloaded from the Gene Expression Omnibus repository. Differentially expressed genes associated with COPD and SCC were identified and visualized using the Advanced Network Merger module in Cytoscape. COPD-associated genes in SCC progression were further identified using the BisoGenet plug-in in Cytoscape. The genetic interaction network was predicted using the Network Analysis function. Heat shock protein 90 α family class A member 1 (), adrenoceptor β2 (), transducin β like 1 X-linked receptor 1 () and heat shock protein family B (small) member 1 () were identified to be differentially expressed in SCC and COPD cases. The overall survival rate associated with the gene signatures was investigated using clinical samples from patients with SCC and COPD from the PROGgene database. The results suggest that the pathogenesis of SCC caused by COPD is regulated by and . These genes may serve as potential therapeutic targets for the treatment of patients with COPD-related SCC. 10.3892/ol.2020.11318
    The relationship between chronic obstructive pulmonary disease and non-small cell lung cancer in the elderly. Wang Peng,Zhu Min,Zhang Dong,Guo Xue-Guang,Zhao Shu,Zhang Xue-Lin,Wang De-Long,Liu Chang-Ting Cancer medicine OBJECTIVES:Chronic obstructive pulmonary disease (COPD) and NSCLC often coexist and have poor prognoses, but studies investigating the impact of COPD on NSCLC have reported inconsistent findings. The objective of this study was to compare survival between NSCLC patients with and without COPD. METHODS:Medical records were retrospectively collected from 301 elderly patients pathologically diagnosed with NSCLC from the Chinese PLA General Hospital. Ultimately, a total of 200 patients were enrolled in the analysis. The survival rates between the COPD-NSCLC and non-COPD NSCLC were assessed using log-rank and Cox proportional hazard regression analyses. RESULTS:A total of 117 COPD-NSCLC and 93 non-COPD NSCLC patients were enrolled in the analysis. The median overall survival times were 108.5 months in the non-COPD group and 45.0 months in the COPD group (HR: 2.05; 95% CI, 1.36-2.97, P = 0.0004). After 118 patients underwent propensity score matching, the median overall survival times were 100.6 months in the non-COPD group and 51.9 months in the COPD group (HR: 1.59; 95% CI, 1.096-2.64, P = 0.0459). The multivariate analysis showed that presence of COPD (HR 1.619, P = 0.030), old age (HR 1.007, P < 00001), an advanced disease stage (stage Ⅲ HR 5.513, P < 0.0001; stage Ⅳ HR 11.743, P < 0.0001), the squamous cell carcinoma histological subtype (HR 3.106, P < 0.0001), the presence of a cough (HR 2.463, P = 0.001) a higher serum carcinoembryonic antigen level (HR 1.001, P = 0.023) and higher NRL (HR 2.615, P = 0.007) were independent factors that were significantly associated with poorer survival. CONCLUSION:A diagnosis of COPD had significant poorer survival outcomes in NSCLC than that of patients without COPD in this elderly population. 10.1002/cam4.2333
    PD-L1, FGFR1, PIK3CA, PTEN, and p16 expression in pulmonary emphysema and chronic obstructive pulmonary disease with resected lung squamous cell carcinoma. Arimura Ken,Sekine Yasuo,Hiroshima Kenzo,Shimizu Satoru,Shibata Noriyuki,Kondo Mitsuko,Takeyama Kiyoshi,Tagaya Etsuko BMC pulmonary medicine BACKGROUND:Emphysema and chronic obstructive pulmonary disease (COPD) are well known independent risk factors for lung cancer. However, the developmental mechanisms between emphysema/COPD and lung cancer remain unknown. The purpose of this study was to evaluate PD-L1, FGFR1, PIK3CA, PTEN, and p16 expression in squamous cell carcinoma (SCC) associated with emphysema/COPD. METHODS:A total of 59 patients with squamous cell lung carcinoma (SCC) resected between 2008 and 2012 were retrospectively reviewed. Emphysema was assessed according to the Goddard score. Total severity was divided into none-mild (0-7), moderate (8-15), and severe (≥ 16). Local severity around the existing tumor was divided into no emphysema (0) and presence of emphysema (1-4). COPD severity was based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. PD-L1, FGFR1, PIK3CA, PTEN, and p16 expression were evaluated by immunohistochemistry (IHC). Expression level was classified as tumor cells (TC) 3 (≥ 50%), TC2 (5-49%), TC1 (1-4%), or TC0 (< 1%), and as tumor-infiltrating immune cells (IC) 3 (≥ 50%), IC2 (5-49%), IC1 (1-4%), or IC0 (< 1%) for PD-L1. Expression level was compared between none-mild/moderate-severe total emphysema, no/presence of local emphysema, no COPD/COPD, and GOLD 1/GOLD 2, 3. RESULTS:PD-L1 expression was significantly correlated with severity of emphysema in TC0, 1, 2 vs. TC3 (P = 0.012). PD-L1 was significantly higher inversely in none-mild emphysema compared to moderate-severe (95% CI, 0.061-5.852, P = 0.045). There were no other significant associations between PD-L1, FGFR1, PIK3CA, PTEN, and p16 expression and total/local severity of emphysema or presence of COPD/GOLD stage. CONCLUSIONS:PD-L1 expression in SCC was correlated with severity of emphysema in TC0, 1, 2 vs. TC3 and more frequent in none-mild emphysema than moderate-severe emphysema. 10.1186/s12890-019-0913-8
    Effect of annual influenza vaccination on reducing lung cancer in patients with chronic obstructive pulmonary disease from a population-based cohort study. Chen Kuan-Yuan,Wu Sheng-Ming,Liu Ju-Chi,Lee Kang-Yun Medicine Chronic obstructive pulmonary disease (COPD) patients are at a higher risk of development of lung cancer. Frequent exacerbations of COPD trigger the disease course to chronic inflammation which likely plays a role in the pathogenesis of lung cancer. Previous studies showed influenza virus infection is one of important causes for exacerbations of COPD. Therefore, the aim of this study was to know whether influenza vaccination could reduce the incidence of lung cancer in patients with COPD.This cohort study enrolled patients (≥55 years old) with a recorded diagnosis of COPD between January 1, 2000 and December 31, 2012 by using the Taiwan Health Insurance Database. A propensity score was calculated to reduce vaccine therapy selection bias. Cox proportional hazard regressions were used to investigate the association between the influenza vaccination and lung cancer incidence after adjusting for known confounding factors. Besides, we categorized the patients into 4 groups according to vaccination status (unvaccinated, total number of vaccinations: 1, 2-3, ≥4) to evaluate the dose-dependent effect on reducing lung cancer occurrence of lung cancer in COPD patients.Our study comprised of 28,752 eligible individuals from the COPD cohort database. Among them, 51% (14,630) received influenza vaccination; the rest (49%) of the COPD patients did not receive influenza vaccination. We observed that COPD patients receiving influenza vaccination had a lower risk of lung cancer (adjusted HR = 0.40, 95% CI (0.35-0.45), P < .001). We also founded comparable protective effect in both sexes and all age groups (55-64, 65-74, ≥75) regardless of influenza seasonality. Furthermore, dose-dependent protective effect could be seen after stratifying patients according to the total number vaccinations, the adjusted HRs for lung cancer risk were 0.48 (0.40-0.54) and 0.24 (0.20-0.29) for patients who received 2 to 3 and ≥4 vaccinations during the follow-up period.This population-based cohort study demonstrated that annual influenza vaccination administration could reduce incidence of lung cancer in COPD patients. 10.1097/MD.0000000000018035
    Chronic obstructive pulmonary disease and comorbidities' influence on mortality in non-small cell lung cancer patients. Media Ara Shwan,Persson Martin,Tajhizi Navid,Weinreich Ulla Møller Acta oncologica (Stockholm, Sweden) In Denmark, lung cancer is the most common cause of cancer-related death and chronic obstructive pulmonary disease (COPD) is the most common comorbidity in patients with non-small cell lung cancer (NSCLC). The aim of this study was to investigate the influence of COPD and other common comorbidities on NSCLC mortality. Patients ( = 534) diagnosed with NSCLC at Aalborg University Hospital from 2008-2010 were included retrospectively in this study. Patient records were assessed and the population was dichotomized in COPD and non-COPD subgroups. Comorbidities i.e., ischemic heart disease, hypertension, diabetes mellitus, apoplexia, former malignancy, interstitial lung disease and psychiatric comorbidity were registered and a comorbidity count were calculated. Survival was assessed with log-rank test and uni- and multivariate regression analysis were performed for COPD-status and comorbidity count adjusting for age, gender, BMI, smoking exposure, cancer stage, method of treatment and eastern cooperative cancer group (ECOG) performance status score. Of 534 NSCLC patients included, 470 were divided into COPD and non-COPD subgroups, 70% with COPD (329/470) and 30% without COPD (141/470). Only 32.5% of the patients in the COPD-group had previously diagnosed COPD. Log-rank test did not show statistically significant difference in survival between the COPD and non-COPD groups ( = .215). Multivariate Cox regression analysis did not show statistically significant association between overall 5-year mortality and the presence of COPD (HR-adj = 0.808, 95% CI = 0.612; 1.068) or other comorbidities (HR-adj = 1.101, 95% CI = 0.979; 1.237) when adjusted for age, BMI, gender, smoking exposure, ECOG performance status, treatment and TNM-stage. Our findings do not suggest that COPD nor other common comorbidities are significantly associated with higher mortality in NSCLC patients. 10.1080/0284186X.2019.1612942
    Hypermethylation of Anti-oncogenic MicroRNA 7 is Increased in Emphysema Patients. Rosas-Alonso Rocío,Galera Raúl,Sánchez-Pascuala Joan José,Casitas Raquel,Burdiel Miranda,Martínez-Cerón Elisabet,Vera Olga,Rodriguez-Antolin Carlos,Pernía Olga,De Castro Javier,García-Rio Francisco,Ibanez-de-Cáceres Inmaculada Archivos de bronconeumologia INTRODUCTION:MicroRNA-7 (miR-7) has a suppressive role in lung cancer and alterations in its DNA methylation may contribute to tumorigenesis. As COPD patients with emphysema have a higher risk of lung cancer than other COPD phenotypes, we compared the miR-7 methylation status among smoker subjects and patients with various COPD phenotypes to identify its main determinants. METHODS:30 smoker subjects without airflow limitation and 136 COPD patients without evidence of cancer were recruited in a prospective study. Clinical and functional characteristics were assessed and patients were classified into: frequent exacerbator, emphysema, chronic bronchitis and asthma COPD overlap (ACO). DNA collected from buccal epithelial samples was isolated and bisulfite modified. miR-7 methylation status was evaluated by quantitative methylation-specific polymerase chain reaction (qMSP). RESULTS:miR-7 Methylated levels were higher in COPD patients than in smokers without airflow limitation (23.7±12.4 vs. 18.5±8.8%, p=0.018). Among COPD patients, those with emphysema had higher values of methylated miR-7 (27.1±10.2%) than those with exacerbator (19.4±9.9%, p=0.004), chronic bronchitis (17.3±9.0%, p=0.002) or ACO phenotypes (16.0±7.2%, p=0.010). After adjusting for clinical parameters, differences between emphysematous patients and those with other phenotypes were retained. In COPD patients, advanced age, mild-moderate airflow limitation, reduced diffusing capacity and increased functional residual capacity were identified as independent predictors of methylated miR-7 levels. CONCLUSION:The increase of miR-7 methylation levels experienced by COPD patients occurs mainly at the expense of the emphysema phenotype, which might contribute to explain the higher incidence of lung cancer in these patients. 10.1016/j.arbres.2019.10.017
    Influence of Chronic Obstructive Pulmonary Disease on Volatile Organic Compounds in Patients with Non-small Cell Lung Cancer. Muñoz-Lucas María Ángeles,Jareño-Esteban Javier,Gutiérrez-Ortega Carlos,López-Guijarro Pablo,Collado-Yurrita Luis,Quintana-Díaz Manuel,Callol-Sánchez Luis Archivos de bronconeumologia INTRODUCTION:The etiology of lung cancer is multifactorial. Exposure to tobacco smoke and the role played by the carcinogenic compounds that it contains would explain the common association between lung cancer and chronic obstructive pulmonary disease (COPD), a disease which is very much linked to tobacco use. In both diseases, sustained inflammation is caused by increased oxidative stress (for example, lipid peroxidation). This generates low molecular weight substances called volatile organic compounds (VOC) that are excreted during breathing. VOC metabolomics provides an indirect measure of oxidative stress. OBJECTIVE:The aim of this study was to establish the relative influence of COPD on the VOC profile in patients with non-small cell lung cancer (NSCLC), by first studying the possible variation of VOC associated with lung cancer histology. PATIENTS AND METHODS:Exhaled air was tested in 107 NSCLC patients, who were divided into 2groups: NSCLC with COPD and non-COPD with NSCLC. The exhaled air sample was obtained with the BIOVOC® sampler, and transferred to desorption tubes for later analysis by thermal desorption-gas chromatography-mass spectrometry. The VOC analysis showed lineal aldehydes and carboxylic acids. RESULTS AND CONCLUSIONS:No statistically significant differences were found in VOC associated with histology. NSCLC and COPD patients present a 1.7-fold (1.1-2.7) probability of detection of propionic acid (95% CI: 1.22- 6.2) than patients without COPD or NSCLC (P = 0.013). 10.1016/j.arbres.2019.12.023
    Spirometry performed as part of the Manchester community-based lung cancer screening programme detects a high prevalence of airflow obstruction in individuals without a prior diagnosis of COPD. Balata Haval,Harvey Jonathan,Barber Phil V,Colligan Denis,Duerden Rebecca,Elton Peter,Evison Matthew,Greaves Melanie,Howells John,Irion Klaus,Karunaratne Devinda,Mellor Stuart,Newton Tom,Sawyer Richard,Sharman Anna,Smith Elaine,Taylor Ben,Taylor Sarah,Tonge Janet,Walsham Anna,Whittaker James,Vestbo Joergen,Booton Richard,Crosbie Phil A Thorax BACKGROUND:COPD is a major cause of morbidity and mortality in populations eligible for lung cancer screening. We investigated the role of spirometry in a community-based lung cancer screening programme. METHODS:Ever smokers, age 55-74, resident in three deprived areas of Manchester were invited to a 'Lung Health Check' (LHC) based in convenient community locations. Spirometry was incorporated into the LHCs alongside lung cancer risk estimation (Prostate, Lung, Colorectal and Ovarian Study Risk Prediction Model, 2012 version (PLCO)), symptom assessment and smoking cessation advice. Those at high risk of lung cancer (PLCO ≥1.51%) were eligible for annual low-dose CT screening over two screening rounds. Airflow obstruction was defined as FEV/FVC<0.7. Primary care databases were searched for any prior diagnosis of COPD. RESULTS:99.4% (n=2525) of LHC attendees successfully performed spirometry; mean age was 64.1±5.5, 51% were women, 35% were current smokers. 37.4% (n=944) had airflow obstruction of which 49.7% (n=469) had no previous diagnosis of COPD. 53.3% of those without a prior diagnosis were symptomatic (n=250/469). After multivariate analysis, the detection of airflow obstruction without a prior COPD diagnosis was associated with male sex (OR 1.84, 95% CI 1.37 to 2.47; p<0.0001), younger age (p=0.015), lower smoking duration (p<0.0001), fewer cigarettes per day (p=0.035), higher FEV/FVC ratio (<0.0001) and being asymptomatic (OR 4.19, 95% CI 2.95 to 5.95; p<0.0001). The likelihood of screen detected lung cancer was significantly greater in those with evidence of airflow obstruction who had a previous diagnosis of COPD (OR 2.80, 95% CI 1.60 to 8.42; p=0.002). CONCLUSIONS:Incorporating spirometry into a community-based targeted lung cancer screening programme is feasible and identifies a significant number of individuals with airflow obstruction who do not have a prior diagnosis of COPD. 10.1136/thoraxjnl-2019-213584
    Inhaled corticosteroids and the risk of lung cancer in COPD: a population-based cohort study. Raymakers Adam J N,Sadatsafavi Mohsen,Sin Don D,FitzGerald J Mark,Marra Carlo A,Lynd Larry D The European respiratory journal Inhaled corticosteroids (ICSs) are often prescribed in patients with chronic obstructive pulmonary disease (COPD). Their impact on the risk of lung cancer, a leading cause of mortality in COPD patients, remains uncertain.Population-based linked administrative data between the years 1997 and 2007 from the province of British Columbia, Canada, were used to evaluate the association between lung cancer risk and ICS use in COPD patients. COPD was defined on the basis of receipt of three COPD-related prescriptions in subjects ≥50 years of age. Exposure to ICS was incorporated into multivariable Cox regression models using several time-dependent methods ("ever" exposure, cumulative duration of use, cumulative dose, weighted cumulative duration of use and weighted cumulative dose).There were 39 676 patients who met the inclusion criteria. The mean±sd age of the cohort was 70.7±11.1 years and 53% were female. There were 994 (2.5%) cases of lung cancer during follow-up. In the reference case analysis (time-dependent "ever" exposure), ICS exposure was associated with a 30% reduced risk of lung cancer (HR 0.70 (95% CI 0.61-0.80)). ICS exposure was associated with a decrease in the risk of lung cancer diagnosis over all five methods of quantifying exposure.This population-based study suggests that ICS use reduces the risk of lung cancer in COPD patients. 10.1183/13993003.01257-2018
    Chronic obstructive pulmonary disease in patients with lung cancer: prevalence, impact and management challenges. Spyratos Dionisios,Papadaki Eleni,Lampaki Sofia,Kontakiotis Theodoros Lung Cancer (Auckland, N.Z.) Chronic obstructive pulmonary disease (COPD) and lung cancer share a common etiological factor (cigarette smoking) and usually coexist in everyday clinical practice. The prevalence of COPD among newly diagnosed patients with lung cancer sometimes exceeds 50%. COPD is an independent risk factor (2-4 times higher than non-COPD subjects) for lung cancer development. The presence of emphysema in addition to other factors (e.g., smoking history, age) could be incorporated into risk scores in order to define the most appropriate target group for lung cancer screening using low-dose computed tomography. Clinical management of patients with coexistence of COPD and lung cancer requires a multidisciplinary oncology board that includes a pulmonologist. Detailed evaluation (lung function tests, cardiopulmonary exercise test) and management (inhaled drugs, smoking cessation, pulmonary rehabilitation) of COPD should be taken into account for lung cancer treatment (surgical approach, radiotherapy). 10.2147/LCTT.S117178
    Genomic mechanisms of transformation from chronic obstructive pulmonary disease to lung cancer. Wang Diane C,Shi Lin,Zhu Zhenhua,Gao Danyan,Zhang Yong Seminars in cancer biology Genetic variations in COPD and lung cancer may be one of the molecular mechanisms responsible for COPD-lung cancer transformation. The present review highlights main genetic variations co-existed in COPD and lung cancer and integrates the varied genes into four molecular mechanisms, e.g. activated cell proliferation pathway, tumor suppressor and DNA repair gene dysfunction, chronic inflammatory microenvironment, and impaired immune response, by which COPD epithelial cells may be transformed into tumorigenic status. We call special attention to further investigate the transformation from COPD to lung cancer and understand the exact molecular mechanisms, to prevent and reduce the increased incidence of COPD and lung cancer. We call direct evidence to show the existence of COPD-lung cancer transformation, since current evidence to support the transformation from COPD to lung cancer is the co-existence of selected genes and proteins in both. We should furthermore explore and understand the homogeneity and heterogeneity of gene mutation, epigenetics, sequencing, and function between COPD and lung cancer. The defining and understanding of COPD-lung cancer transformation will provide new diagnostic and therapeutic biomarkers as a new milestone to prevent and treat lung cancer. 10.1016/j.semcancer.2016.11.001
    Function of macrophage scavenger receptor 1 gene polymorphisms in chronic obstructive pulmonary disease with and without lung cancer in China. Xie Liang,Chen Wei,Dong Ran,He Bin,Zhao Kaishun,Zhang Li,Zhou Min,He Ping Oncology letters The present study assessed the association between the variants of macrophage scavenger receptor (MSR)1 and chronic obstructive pulmonary disease (COPD), with or without lung cancer in China. COPD and lung cancer were previously regarded as two separate diseases. However, it has since been reported that there are close associations between COPD and lung cancer. Lung cancer may be an outcome of COPD. COPD may also coexist with lung cancer, and patients with COPD with lung cancer tend to have increased mortality. It is important to have a better understanding of the pathogenesis of COPD and the reason why it develops into lung cancer. MSR1 serves a crucial function in phagocytosis, which may be associated with the pathogenesis of COPD and lung cancer in patients with COPD. From 1 July 2015 to 20 February 2016, 100 patients with COPD and lung cancer, 100 patients with COPD without lung cancer and 100 healthy smokers were enrolled at the Shanghai Ruijin Hospital (Shanghai, China) for the genotyping of eight single-nucleotide polymorphisms (SNPs; ex3P36A_C>G, ex3S41Y_C>A, ex4V113A_T>C, ex4P174Y_G>T, ex6P275A_C>G, ex6R293×_C>T, ex10G369S_G>A and ex11H441R_A>G) via gene sequencing. The genotype frequencies of these SNPs did not significantly differ between patients with COPD with and without lung cancer, and the healthy controls. However, during DNA sequencing, the SNP rs13306550 (IVS4+3A>G) was identified in the splice donor site and was significantly associated with an increased risk of COPD compared with the healthy smokers (P=0.0053). The present study demonstrated that the variant rs13306550 was a risk factor for COPD susceptibility, but that did not influence lung cancer pathogenesis in patients with COPD. However, the mechanisms underlying the influence of rs13306550 on COPD development and progression remain to be elucidated and require further study. 10.3892/ol.2018.8311
    Exposing a deadly alliance: novel insights into the biological links between COPD and lung cancer. Vermaelen K,Brusselle G Pulmonary pharmacology & therapeutics Chronic obstructive pulmonary disease (COPD) affects more than 200 million people worldwide and is expected to become the third leading cause of death in 2020. COPD is characterized by progressive airflow limitation, due to a combination of chronic inflammation and remodeling of the small airways (bronchiolitis) and loss of elastic recoil caused by destruction of the alveolar walls (emphysema). Lung cancer is the most important cause of cancer-related death in the world. (Cigarette) smoking is the principal culprit causing both COPD and lung cancer; in addition, exposure to environmental tobacco smoke, biomass fuel smoke, coal smoke and outdoor air pollution have also been associated with an increased incidence of both diseases. Importantly, smokers with COPD--defined as either not fully reversible airflow limitation or emphysema--have a two- to four-fold increased risk to develop lung cancer. In this review, we highlight several of the genetic, epigenetic and inflammatory mechanisms, which link COPD and carcinogenesis in the lungs. Elucidating the biological pathways and networks, which underlie the increased susceptibility of lung cancer in patients with COPD, has important implications for screening, prevention, diagnosis and treatment of these two devastating pulmonary diseases. 10.1016/j.pupt.2013.05.003