Multi-omics comprehensive analysis reveals the predictive value of N6-methyladenosine- related genes in prognosis and immune escape of bladder cancer.

IF 2.2 4区医学 Q3 ONCOLOGY

Cancer Biomarkers Pub Date : 2024-01-01 DOI:10.3233/CBM-230286

Yang Liu, Zhongqi Pang, Jianshe Wang, Jinfeng Wang, Bo Ji, Yidan Xu, Jiaxin He, Lu Zhang, Yansong Han, Linkun Shen, Wanhai Xu, Minghua Ren

{"title":"Multi-omics comprehensive analysis reveals the predictive value of N6-methyladenosine- related genes in prognosis and immune escape of bladder cancer.","authors":"Yang Liu, Zhongqi Pang, Jianshe Wang, Jinfeng Wang, Bo Ji, Yidan Xu, Jiaxin He, Lu Zhang, Yansong Han, Linkun Shen, Wanhai Xu, Minghua Ren","doi":"10.3233/CBM-230286","DOIUrl":null,"url":null,"abstract":"Background: N6-methyladenosine (m6A) is the most frequent RNA modification in mammals, and its role in bladder cancer (BC) remains rarely revealed.Objective: To predict the value of m6A-related genes in prognosis and immunity in BC.Methods: We performed multiple omics analysis of 618 TCGA and GEO patients and used principal component analysis (PCA) to calculate the m6A score for BC patients.Results: We described the multiple omics status of 23 m6A methylation-related genes (MRGs), and four m6A clusters were identified, which showed significant differences in immune infiltration and biological pathways. Next, we intersected the differential genes among m6A clusters, and 11 survival-related genes were identified, which were used to calculate the m6A score for the patients. We found that the high-score (HS) group showed lower tumor mutation burden (TMB) and TP53 mutations and better prognosis than the low-score (LS) group. Lower immune infiltration, higher expression of PD-L1, PD-1, and CTLA4, and higher immune dysfunction and immune exclusion scores were identified in the LS group, suggesting a higher possibility of immune escape. Finally, the experimental verification shows that the m6A related genes, such as IGFBP1, plays an important role in the growth and metastasis of bladder cancer.Conclusions: These findings revealed the important roles of m6A MRGs in predicting prognosis, TMB status, TP53 mutation, immune functions and immunotherapeutic response in BC.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":" ","pages":"79-94"},"PeriodicalIF":2.2000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11307005/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Biomarkers","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3233/CBM-230286","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: N6-methyladenosine (m6A) is the most frequent RNA modification in mammals, and its role in bladder cancer (BC) remains rarely revealed.

Objective: To predict the value of m6A-related genes in prognosis and immunity in BC.

Methods: We performed multiple omics analysis of 618 TCGA and GEO patients and used principal component analysis (PCA) to calculate the m6A score for BC patients.

Results: We described the multiple omics status of 23 m6A methylation-related genes (MRGs), and four m6A clusters were identified, which showed significant differences in immune infiltration and biological pathways. Next, we intersected the differential genes among m6A clusters, and 11 survival-related genes were identified, which were used to calculate the m6A score for the patients. We found that the high-score (HS) group showed lower tumor mutation burden (TMB) and TP53 mutations and better prognosis than the low-score (LS) group. Lower immune infiltration, higher expression of PD-L1, PD-1, and CTLA4, and higher immune dysfunction and immune exclusion scores were identified in the LS group, suggesting a higher possibility of immune escape. Finally, the experimental verification shows that the m6A related genes, such as IGFBP1, plays an important role in the growth and metastasis of bladder cancer.

Conclusions: These findings revealed the important roles of m6A MRGs in predicting prognosis, TMB status, TP53 mutation, immune functions and immunotherapeutic response in BC.

查看原文本刊更多论文

多组学综合分析揭示了N6-甲基腺苷相关基因在膀胱癌预后和免疫逃逸中的预测价值。

背景：N6-甲基腺苷（m6A）是哺乳动物体内最常见的RNA修饰，但其在膀胱癌（BC）中的作用却很少被揭示：预测m6A相关基因在膀胱癌预后和免疫中的价值：我们对618例TCGA和GEO患者进行了多组学分析，并使用主成分分析法（PCA）计算了BC患者的m6A得分：结果：我们描述了23个m6A甲基化相关基因（MRGs）的多组学状态，发现了4个m6A集群，它们在免疫浸润和生物通路方面存在显著差异。接下来，我们对m6A群组间的差异基因进行了交叉分析，发现了11个与生存相关的基因，并以此计算出患者的m6A得分。我们发现，与低分（LS）组相比，高分（HS）组的肿瘤突变负荷（TMB）和TP53突变较低，预后较好。LS组免疫浸润较低，PD-L1、PD-1和CTLA4表达较高，免疫功能紊乱和免疫排斥评分较高，提示免疫逃逸的可能性较大。最后，实验验证表明，m6A相关基因（如IGFBP1）在膀胱癌的生长和转移中发挥着重要作用：这些发现揭示了 m6A MRGs 在预测膀胱癌预后、TMB 状态、TP53 突变、免疫功能和免疫治疗反应方面的重要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cancer Biomarkers ONCOLOGY-

CiteScore

5.20

自引率

3.20%

发文量

195

审稿时长

3 months

期刊介绍： Concentrating on molecular biomarkers in cancer research, Cancer Biomarkers publishes original research findings (and reviews solicited by the editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion. The disease markers may include, but are not limited to, genomic, epigenomic, proteomics, cellular and morphologic, and genetic factors predisposing to the disease or indicating the occurrence of the disease. Manuscripts on these factors or biomarkers, either in altered forms, abnormal concentrations or with abnormal tissue distribution leading to disease causation will be accepted.