Perineural invasion-associated biomarkers for tumor development.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Perineural invasion (PNI) is the process of neoplastic invasion of peripheral nerves and is considered to be the fifth mode of cancer metastasis. PNI has been detected in head and neck tumors and pancreatic, prostate, bile duct, gastric, and colorectal cancers. It leads to poor prognostic outcomes and high local recurrence rates. Despite the increasing number of studies on PNI, targeted therapeutic modalities have not been proposed. The identification of PNI-related biomarkers would facilitate the non-invasive and early diagnosis of cancers, the establishment of prognostic panels, and the development of targeted therapeutic approaches. In this review, we compile information on the molecular mediators involved in PNI-associated cancers. The expression and prognostic significance of molecular mediators and their receptors in PNI-associated cancers are analyzed, and the possible mechanisms of action of these mediators in PNI are explored, as well as the association of cells in the microenvironment where PNI occurs.
10.1016/j.biopha.2022.113691
Tumour-infiltrating B cells: immunological mechanisms, clinical impact and therapeutic opportunities.
Nature reviews. Cancer
Although immunotherapy research to date has focused largely on T cells, there is mounting evidence that tumour-infiltrating B cells and plasma cells (collectively referred to as tumour-infiltrating B lymphocytes (TIL-Bs)) have a crucial, synergistic role in tumour control. In many cancers, TIL-Bs have demonstrated strong predictive and prognostic significance in the context of both standard treatments and immune checkpoint blockade, offering the prospect of new therapeutic opportunities that leverage their unique immunological properties. Drawing insights from autoimmunity, we review the molecular phenotypes, architectural contexts, antigen specificities, effector mechanisms and regulatory pathways relevant to TIL-Bs in human cancer. Although the field is young, the emerging picture is that TIL-Bs promote antitumour immunity through their unique mode of antigen presentation to T cells; their role in assembling and perpetuating immunologically 'hot' tumour microenvironments involving T cells, myeloid cells and natural killer cells; and their potential to combat immune editing and tumour heterogeneity through the easing of self-tolerance mechanisms. We end by discussing the most promising approaches to enhance TIL-B responses in concert with other immune cell subsets to extend the reach, potency and durability of cancer immunotherapy.
10.1038/s41568-022-00466-1
Cuproptosis correlates with immunosuppressive tumor microenvironment based on pan-cancer multiomics and single-cell sequencing analysis.
Molecular cancer
Recent studies suggest that cuproptosis, a novel mode of cell death, may be associated with the development of cancer. However, no studies are showing its role in tumorigenesis, progression, and prognosis. In the present study, we comprehensively analyzed the expression difference, gene variation and methylation modification of cuproptosis-related genes (CRGs) in pan-cancer. Then, Single sample gene set enrichment analysis (ssGSEA) was used to calculate individual cuproptosis scores (CS). The association of CS with copy number variation, clinical features, immune-related genes, TMB, MSI, and tumor immune dysfunction and exclusion (TIDE) was comprehensively assessed. Single-cell transcriptome sequencing (scRNA-seq) to analyze the activation of cuproptosis in the tumor microenvironment. Immunohistochemistry (IHC) were used to validate the expression of cuproptosis hub-gene. Our study shows that CRGs were significantly expressed in a variety of tumors, and CDKN2A had the highest mutation frequency (49%) in all tumors. A significant increase in the CS was observed in most cancers and were associated with poor prognosis in the majority of tumors. CS was significantly negatively correlated with tumor microenvironment scores in more than 10 tumors and positively correlated with PD-L1 in 11 tumors, suggesting involvement in tumor immune escape. scRNA-seq suggests that CRG scores significantly increased in the cancer cells. This study opens avenues for further research on the role of cuproptosis in the occurrence and development of cancer and the development of targeted therapies based on cuproptosis.
10.1186/s12943-023-01752-8
Correlation between Ferroptosis-Related Gene Signature and Immune Landscape, Prognosis in Breast Cancer.
Journal of immunology research
Breast cancer (BC) is the most commonly diagnosed cancer and second leading cause of cancer-related death in women worldwide. Ferroptosis, an iron-dependent newly discovered mode of cell death, can be induced by lenaltinib and plays an important role in the biological behaviors of BC. Therefore, the prognostic value of ferroptosis-related genes (FRGs) in BC warrants further investigation. FRG expression profiles and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO). Immune-related pathways were found in the functional analysis. Significant differences in enrichment scores for immune cells were observed. Some patients from TCGA-BRCA were included as the training cohort. A six-gene prediction signature was constructed with the least absolute shrinkage and selection operator Cox regression. This model was validated in the rest of the TCGA-BRCA and GEO cohort. The expressions of the six FRGs were verified with real-time quantitative polymerase chain reaction and immunohistochemistry in the Human Protein Atlas. Relapse or metastasis was more likely in the high-risk group. Risk score was an independent predictor of disease-free survival. Collectively, the ferroptosis-related risk model established in this study may serve as an effective tool to predict the prognosis in BC.
10.1155/2022/6871518
Incidence, prognostic factors and a nomogram of cervical cancer with distant organ metastasis: a SEER-based study.
Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology
This study was to investigate the incidence, survival and prognostic factors of cervical cancer with distant organ metastasis, and to develop a nomogram to predict the prognosis of cervical cancer. We used the Surveillance, Epidemiology and End Results (SEER) database to screen patients diagnosed with cervical cancer from 2010 to 2014. The chi-squared test was used to analyse the differences in clinical characteristics, and we used Kaplan-Meier methods to perform survival analysis. Univariate and multivariate Cox proportional hazard regression models were used to estimate prognostic factors, and we developed a visual nomogram to judge the prognosis. We found that lung metastasis was the most common in cervical cancer patients with distant organ metastasis. Age, race, characteristics of the tumour, and therapy should be considered when analysing the prognosis of cervical cancer patients. The findings of this study may help clinicians to formulate individualised treatment strategies.Impact Statement Distant organ metastasis of cervical cancer mainly involves lung, bone, liver and brain. Once it occurs, the survival and prognosis will be threatened seriously. 4176 patients were included, and lung metastasis was the most common in cervical cancer with distant organ metastasis (3.5%). Additionally, age, race, tumour grade, histological type, T-stage, N-stage, lung, liver and bone metastasis and the treatment mode are significantly related to the outcomes of cervical cancer patients. Furthermore, we developed a nomogram that could predict the probability of three-year and five-year OS. The findings of this study may drive more and more studies focussing on the comprehensive prognostic assessment, diagnosis, and treatment of distant metastasis of cervical cancer. Besides, clinicians can utilise these findings to formulate individualised treatment strategies.
10.1080/01443615.2023.2181690
Tumour-related factors and prognosis in breast cancer detected by screening.
Olsson A,Borgquist S,Butt S,Zackrisson S,Landberg G,Manjer J
The British journal of surgery
BACKGROUND:Breast cancer detected by screening has an unexplained prognostic advantage beyond stage shift compared with cancers detected clinically. The aim was to investigate biological factors in invasive breast cancer, with reference to mode of detection and rate of death from breast cancer. METHODS:Histology, oestrogen receptor α and β, progesterone receptor, human epidermal growth factor receptor (HER) 2, cyclin D1, p27, Ki-67 and perinodal growth were analysed in 466 tumours from a prospective cohort, the Malmö Diet and Cancer Study. Using logistic regression, odds ratios were calculated to investigate the relationship between tumour characteristics and mode of detection. The same tumour factors were analysed in relation to standard prognostic features. Death from breast cancer was analysed using Cox regression with adjustments for standard tumour factors; differences following adjustment were analysed by means of Freedman statistics. RESULTS:None of the biological tumour characteristics varied with mode of detection of breast cancer. After adjustment for age, tumour size, axillary lymph node involvement (ALNI) and grade, women with cancer detected clinically had an increased risk of death from breast cancer (hazard ratio 2·48, 95 per cent confidence interval 1·34 to 4·59), corresponding to a 37·2 per cent difference compared with the unadjusted model. Additional adjustment for biological tumour factors studied caused only minor changes. CONCLUSION:None of the biological tumour markers investigated explained the improved prognosis in breast cancer detected by screening. None of the factors was related to ALNI, suggesting that other mechanisms may be responsible for tumour spread.
10.1002/bjs.7757
Prognostic significance of preoperative neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in patients with gallbladder carcinoma.
Zhang Y,Jiang C,Li J,Sun J,Qu X
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
PURPOSE:Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were immune response-related indicators. Preoperative NLR and PLR had been considered to be related to the prognosis of various cancers. The objective of this study was to evaluate the prognostic significance of NLR and PLR in patients with gallbladder carcinoma (GBC). METHODS:From 2001 to 2013, 145 patients with GBC were recruited in this retrospective study. Cutoff values of NLR and PLR were determined by receiver operating characteristic curves (ROC). The correlation of clinical data, including tumor differentiation, nevin stage, TNM stage, operation margin, operation mode, NLR, PLR, hemoglobin, C reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 199 (CA199) with median survival period of patients was analyzed by univariate survival analysis. The multivariate prognosis analysis was performed to select the independent prognostic factors. RESULTS:The cutoff values of NLR and PLR were 1.94 and 113.34, respectively. Compared with low NLR and low PLR group, the 5-year survival rates in high NLR and high PLR group were reduced (P < 0.05). The degree of tumor differentiation, nevin stage, TNM stage, operation mode, NLR, PLR, CA199, total bilirubin, CRP and CEA were associated with the median survival period of patients (P < 0.01). The multivariate prognosis analysis showed that NLR, nevin stage, operation mode and hemoglobin were independent prognostic factors (P < 0.05). CONCLUSION:Preoperative NLR and PLR were closely related to prognosis of patients with GBC and might be useful for the evaluation of prognosis of patients with GBC.
10.1007/s12094-015-1310-2
Mode of detection: an independent prognostic factor for women with breast cancer.
Hofvind Solveig,Holen Åsne,Román Marta,Sebuødegård Sofie,Puig-Vives Montse,Akslen Lars
Journal of medical screening
OBJECTIVES:To investigate breast cancer survival and risk of breast cancer death by detection mode (screen-detected, interval, and detected outside the screening programme), adjusting for prognostic and predictive tumour characteristics. METHODS:Information about detection mode, prognostic (age, tumour size, histologic grade, lymph node status) and predictive factors (molecular subtypes based on immunohistochemical analyses of hormone receptor status (estrogen and progesterone) and Her2 status) were available for 8344 women in Norway aged 50-69 at diagnosis of breast cancer, 2005-2011. A total of 255 breast cancer deaths were registered by the end of 2011. Kaplan-Meier method was used to estimate six years breast cancer specific survival and Cox proportional hazard model to estimate hazard ratio (HR) for breast cancer death by detection mode, adjusting for prognostic and predictive factors. RESULTS:Women with screen-detected cancer had favourable prognostic and predictive tumour characteristics compared with interval cancers and those detected outside the screening programme. The favourable characteristics were present for screen-detected cancers, also within the subtypes. Adjusted HR of dying from breast cancer was two times higher for women with symptomatic breast cancer (interval or outside the screening), using screen-detected tumours as the reference. CONCLUSIONS:Detection mode is an independent prognostic factor for women diagnosed with breast cancer. Information on detection mode might be relevant for patient management to avoid overtreatment.
10.1177/0969141315604006
Exploration of the prognostic effect of costimulatory genes in bladder cancer.
The journal of gene medicine
BACKGROUND:A prognostic model of bladder cancer was constructed based on costimulatory molecules, and its stability and accuracy were verified in different datasets. METHOD:The expression profile of bladder cancer RNA and the corresponding clinical data in The Cancer Genome Atlas (TCGA) database were analyzed employing computational biology, and a prognostic model was constructed for costimulating molecule-related genes. The model was applied in GSE160693, GSE176307, Xiangya_Cohort, GSE13507, GSE19423, GSE31684, GSE32894, GSE48075, GSE69795 and GSE70691 in TCGA dataset and Gene Expression Omnibus database. The role of costimulating molecules in bladder cancer tumor subtypes was also explored. By consistent cluster analysis, bladder cancer in the TCGA dataset was categorized into two subtypes: C1 and C2. The C1 subtype exhibited a poor prognosis, high levels of immune cell infiltration and significant enrichment of natural killer cells, T cells and dendritic cells in the C1 subtype. In addition, the ImmuneScore calculated by the ESTIMATE algorithm differed greatly between the two subtypes, and the ImmuneScore of the C1 subtype was greater than the C2 subtype in a significant manner. RESULTS:This study also assessed the relationship between costimulating molecules and immunotherapy response. The high-risk group responded poorly to immunotherapy, with significant differences in the amount of most immune cells between the two groups. Further, three indices of the ESTIMATE algorithm and 22 immune cells of the CIBERSORT algorithm were significantly correlated with risk values. These findings suggest the potential value of costimulating molecules in predicting immunotherapy response. CONCLUSION:A costimulatory molecule-based prognostic model for bladder cancer was established and validated across multiple datasets. This model introduces a novel mode for tailoring treatments to each individual with bladder cancer, and offers valuable insights for informed clinical choices. Simultaneously, this research also delved into the significance of costimulating molecules within distinct bladder cancer subtypes, shedding novel insights into improving immunotherapy strategies for the treatment of bladder cancer.
10.1002/jgm.3655
Comprehensive analysis of bulk and single-cell transcriptomic data reveals a novel signature associated with endoplasmic reticulum stress, lipid metabolism, and liver metastasis in pancreatic cancer.
Journal of translational medicine
BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with high probability of recurrence and distant metastasis. Liver metastasis is the predominant metastatic mode developed in most pancreatic cancer cases, which seriously affects the overall survival rate of patients. Abnormally activated endoplasmic reticulum stress and lipid metabolism reprogramming are closely related to tumor growth and metastasis. This study aims to construct a prognostic model based on endoplasmic reticulum stress and lipid metabolism for pancreatic cancer, and further explore its correlation with tumor immunity and the possibility of immunotherapy. METHODS:Transcriptomic and clinical data are acquired from TCGA, ICGC, and GEO databases. Potential prognostic genes were screened by consistent clustering and WGCNA methods, and the whole cohort was randomly divided into training and testing groups. The prognostic model was constructed by machine learning method in the training cohort and verified in the test, TCGA and ICGC cohorts. The clinical application of this model and its relationship with tumor immunity were analyzed, and the relationship between endoplasmic reticulum stress and intercellular communication was further explored. RESULTS:A total of 92 characteristic genes related to endoplasmic reticulum stress, lipid metabolism and liver metastasis were identified in pancreatic cancer. We established and validated a prognostic model for pancreatic cancer with 7 signatures, including ADH1C, APOE, RAP1GAP, NPC1L1, P4HB, SOD2, and TNFSF10. This model is considered to be an independent prognosticator and is a more accurate predictor of overall survival than age, gender, and stage. TIDE score was increased in high-risk group, while the infiltration levels of CD8 T cells and M1 macrophages were decreased. The number and intensity of intercellular communication were increased in the high ER stress group. CONCLUSIONS:We constructed and validated a novel prognostic model for pancreatic cancer, which can also be used as an instrumental variable to predict the prognosis and immune microenvironment. In addition, this study revealed the effect of ER stress on cell-cell communication in the tumor microenvironment.
10.1186/s12967-024-05158-y