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    Acetyl Coenzyme A Synthase 2 Acts as a Prognostic Biomarker Associated with Immune Infiltration in Cervical Squamous Cell Carcinoma. Li Chia-Jung,Chiu Yi-Han,Chang Chung,Chang Yuan-Chin Ivan,Sheu Jim Jinn-Chyuan,Chiang An-Jen Cancers Cervical squamous cell carcinoma (CESC) is one of the most common malignant tumors in women worldwide with a low survival rate. Acetyl coenzyme A synthase 2 (ACSS2) is a conserved nucleosidase that converts acetate to acetyl-CoA for energy production. Our research intended to identify the correlations of ACSS2 with clinical prognosis and tumor immune infiltration in CESC. ACSS2 is highly expressed in many tumors and is involved in the progression and metastasis of these tumors. However, it is not clear how ACSS2 affects CESC progression and immune infiltration. Analysis of the cBioPortal, GEPIA2, UALCAN, and TCGA databases showed that ACSS2 transcript levels were significantly upregulated in multiple cancer types including CESC. Quantitative RT-PCR analysis confirmed that ACSS2 expression was significantly upregulated in human cervical cancer cells. Here, we performed tissue microarray analysis of paraffin-embedded tissues from 240 cervical cancer patients recorded at FIGO/TNM cancer staging. The results showed that ACSS2 and PDL1 were highly expressed in human CESC tissues, and its expression was associated with the clinical characteristics of CESC patients. TIMER database analysis showed that ACSS2 expression in CESC was associated with tumor infiltration of B cells, CD4+ and CD8+ T cells, and cancer-associated fibroblasts (CAF). Kaplan-Meier survival curve analysis showed that CESC with high ACSS2 expression was associated with shorter overall survival. Collectively, our findings establish ACSS2 as a potential diagnostic and prognostic biomarker for CESC. 10.3390/cancers13133125
    Comprehensive Analysis of HDAC Family Identifies as a Prognostic and Immune Infiltration Indicator and -Related Signature for Prognosis in Glioma. Fan Yuxiang,Peng Xinyu,Wang Yubo,Li Baoqin,Zhao Gang Frontiers in molecular biosciences The histone deacetylase (HDAC) family limited accessibility to chromatin containing tumor suppressor genes by removing acetyl groups, which was deemed a path for tumorigenesis. Considering glioma remained one of the most common brain cancers with a dichotomy prognosis and limited therapy responses, HDAC inhibitors were an area of intensive research. However, the expression profiles and prognostic value of the HDACs required more elucidation. Multiple biomedical databases were incorporated, including ONCOMINE, GEPIA, TCGA, CGGA, GEO, TIMER, cBioPortal, and Metascape, to study expression profiles, prognostic value, immune infiltration, mutation status, and enrichment of HDACs in glioma. STRING and GeneMANIA databases were used to identify -related molecules. LASSO regression, Cox regression, Kaplan-Meier plot, and receiver operating characteristic (ROC) analyses were performed for -related signature construction and validation. was significantly overexpressed in glioma, while was downregulated in glioblastoma. Except for , the HDAC family expression was significantly associated with glioma grade. Most of the HDAC family also correlated with glioma genetic mutations. Higher expression level predicted more dismal overall survival (OS) ( < 0.0001) and disease-free survival (DFS) ( < 0.0001), but a higher level of held more favorable OS ( = 2.1e-14) and DFS ( = 4.8e-08). displayed the highest mutation ratio, at 2.6% of the family. The prognostic value of was validated with ROC achieving 0.70, 0.77, 0.75, and 0.80 as separability for 1-, 3-, 5-, and 10-years OS predictions in glioma, respectively. Moreover, expression positively correlated with neutrophil (r = 0.60, = 2.88e-47) and CD4 T cell infiltration (r = 0.52, = 3.96e-35) in lower-grade glioma. The final -related signature comprised of , (Hazard Ratio:1.49, 95%Confidence Interval:1.20-1.86), , , and , and was verified by survival analysis ( < 0.0001) and ROC with 0.80, 0.84, 0.83, and 0.88 as separability for 1-, 3-, 5-, and 10-years OS predictions, respectively. The signature was enriched in chromatin binding. HDAC family was of clinical significance for glioma. Most of the HDAC family significantly correlated with the glioma grade, mutation, and codeletion. was both a prognostic and immune infiltration indicator and a central component of the -related signature for precise prognosis prediction in glioma. 10.3389/fmolb.2021.720020
    Comprehensive Analysis of Acetylation-Related lncRNAs and Identified AC099850.3 as Prognostic Biomarker in Non-Small Cell Lung Cancer. Zhou Junliang,Zhang Mingyan,Dong Huanhuan,Wang Meiqi,Cheng Yue,Wang Shuqing,Ma Wenbo,Xu Hui Journal of oncology The present study aimed to analyze the effects of acetylation-related lncRNAs in non-small-cell lung cancer (NSCLC). A total of 399 differentially expressed lncRNAs (DElncRNAs) have been identified between 497 NSCLC tissues and 54 normal tissues in the TCGA database, and 105 of which were correlated with acetylation regulators. By using univariate cox regression analysis and combining it with clinical prognosis information, 12 prognostic-related lncRNAs were selected for the subsequent analysis. The NSCLC patients were divided into two subgroups (cluster 1 and cluster 2) by clustering software, and immunocyte infiltration analysis, microenvironmental analysis, and clinical relevance analysis were performed between the two subgroups. A risk model was also built to further assess the prognosis value of prognostic-related lncRNAs in NSCLC patients. We found that AC099850.3 was significantly higher in both cluster 1 and high-risk subgroups, which may serve as a potential biomarker for the prognosis of NSCLC patients. Then, based on ceRNA competition mechanisms, the pathway enrichment of 105 acetylation-related lncRNAs was conducted by GO and KEGG analyses. We found the acetylation-related lncRNAs were primarily enriched in MAPK and EGFR signaling pathways, which were closely associated with NSCLC development. Finally, we validated the expression levels of AC099850.3 in NSCLC tissues and adjacent non-cancerous tissues and confirmed that AC099850.3 was significantly highly expressed in NSCLC tissues and cells. These results may provide clues for our understanding of the role of acetylation-related lncRNAs and valuable information for future clinical diagnosis and prognosis in NSCLC patients. 10.1155/2021/4405697
    Development and Validation of a Novel Histone Acetylation-Related Gene Signature for Predicting the Prognosis of Ovarian Cancer. Dai Qinjin,Ye Ying Frontiers in cell and developmental biology Histone acetylation is one of the most common epigenetic modifications, which plays an important role in tumorigenesis. However, the prognostic role of histone acetylation-regulators in ovarian cancer (OC) remains little known. We compared the expression levels of 40 histone acetylation-related genes between 379 OC samples and 88 normal ovarian tissues and identified 37 differently expressed genes (DEGs). We further explored the prognostic roles of these DEGs, and 8 genes were found to be correlated with overall survival ( < 0.1). In the training stage, an 8 gene-based signature was conducted by the least absolute shrinkage and selector operator (LASSO) Cox regression. Patients in the training cohort were divided into two risk subgroups according to the risk score calculated by the 8-gene signature, and a notable difference of OS was found between the two subgroups ( < 0.001). The 8-gene risk model was then verified to have a well predictive role on OS in the external validation cohort. Combined with the clinical characteristics, the risk score was proved to be an independent risk factor for OS. In conclusion, the histone acetylation-based gene signature has a well predictive effect on the prognosis of OC and can potentially be applied for clinical treatments. 10.3389/fcell.2022.793425
    The Prognostic Value of Lysine Acetylation Regulators in Hepatocellular Carcinoma. Sun Liying,Zhang Jian,Wen Kai,Huang Shenglan,Li Dan,Xu Yongkang,Wu Jianbing Frontiers in molecular biosciences Hepatocellular carcinoma (HCC) is a tumor with high morbidity and mortality worldwide. lysine acetylation regulators (LARs) dynamically regulate Lysine acetylation modification which plays an important regulatory role in cancer. Therefore, we aimed to explore the potential clinical prognostic value of LARs in HCC. Differentially expressed LARs in normal liver and HCC tissues were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. To identify genes with prognostic value and establish the risk characteristics of LARs, consensus clustering was employed. We used univariate Cox regression survival analysis and LASSO Cox regression based on LARs to determine the independent prognostic signature of HCC. CIBERSORT and Gene Set Enrichment Analysis (GSEA) were used to estimate immune infiltration and functional enrichment analysis respectively. The expression of LAR was detected by Real-time quantitative polymerase chain reaction (RT-qPCR). statistical analyses were conducted using SPSS and R software. In this study, the 33 LARs expression data and corresponding clinical information of HCC were obtained using TCGA and ICGC datasets. We found majority of the LARs were differentially expressed. Consensus cluster analysis was carried out based on the TCGA cohort, and three HCC subtypes (cluster 1, 2, and 3) were obtained. The LA3 subgroup had the worst clinical outcomes. Nine key LARs were identified to affect prognosis. The results showed that LARs signature has a strong independent prognostic value in HCC patients, whether in the training datasets or in the testing datasets. GSEA results showed that various tumor-related processes and pathways were abundant in the high-risk groups. RT-qPCR results showed that HAT1, HDAC1, HDAC2, HDAC4, and HDAC11 were highly expressed in HCC cells. Our results suggest that LARs play critical roles in HCC and are helpful for individual prognosis monitoring and clinical decision-making of HCC. 10.3389/fmolb.2022.840412