Comprehensive Analysis of Alternative Polyadenylation Events Associated with the Tumor Immune Microenvironment in Colon Adenocarcinoma.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Fangning Pang, Peng Yang, Tongfei Wang, Xuzhao Li, Xiaoyong Wu, Rong Yue, Bin Bai, Qingchuan Zhao
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引用次数: 0

Abstract

Objective: Colon adenocarcinoma (COAD) is one of the leading causes of cancer death worldwide. Alternative polyadenylation (APA) is relevant to the variability of the 3'-UTR of mRNA. However, the posttranscriptional dysregulation of APA in COAD is poorly understood.

Methods: We collected APA data from The Cancer Genome Atlas (TCGA) COAD (n =7692). APA events were evaluated using PDUI values, and the prognostically significant APA events were screened by LASSO Cox regression to construct a prognostic model. Then, prognostic model functions and possible regulatory genes of characteristic APA events were analyzed. Finally, the immune regulatory network based on APA regulatory genes was analyzed and established.

Results: A total of 95 APA events were found to influence the COAD outcomes. Among them, 39 genes were screened as characteristic prognostic APA events by LASSO Cox regression to construct a COAD prognostic signature. The analysis results suggested that a high signature score was associated with poor prognosis and was significantly correlated with a variety of immune cells, including NK and Th1, 2 and 17 cells. Further analysis showed that APA regulators mainly served roles in the prognosis of COAD. Based on the above results, we constructed an immunoregulatory network for APA regulatory genes-APA genes-immune cells.

Conclusion: Our study revealed that APA events in COAD may regulate tumor progression by influencing immune cells, which provides a new direction for exploring the influencing mechanism of the tumor immune microenvironment and is expected to provide a potential new target for COAD immunotherapy.

结肠腺癌中与肿瘤免疫微环境相关的选择性聚腺苷化事件的综合分析
结肠腺癌(COAD)是全球癌症死亡的主要原因之一。选择性多腺苷酸化(APA)与信使核糖核酸3'-UTR的变异性有关。然而,人们对COAD中APA的转录后失调知之甚少。我们从癌症基因组图谱(TCGA)COAD收集APA数据(n=7692)。使用PDUI值评估APA事件,并通过LASSO-Cox回归筛选具有预后意义的APA事件以构建预后模型。然后,分析了特征性APA事件的预后模型功能和可能的调控基因。最后,分析并建立了基于APA调控基因的免疫调控网络。共发现95个APA事件影响COAD结果。其中,39个基因通过LASSO-Cox回归筛选为特征性预后APA事件,构建COAD预后标志。分析结果表明,高标志性得分与预后不良有关,并与多种免疫细胞显著相关,包括NK细胞和Th1、2和17细胞。进一步的分析表明APA调节因子主要在COAD的预后中发挥作用。基于上述结果,我们构建了APA调控基因APA基因免疫细胞的免疫调控网络。我们的研究表明,COAD中的APA事件可能通过影响免疫细胞来调节肿瘤进展,这为探索肿瘤免疫微环境的影响机制提供了新的方向,有望为COAD免疫治疗提供潜在的新靶点。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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