Objective: Alternative polyadenylation (APA) is a common mechanism that is present in most human genes and determines the length of the messenger ribonucleic acid (mRNA) three prime untranslated region (3ʹ-UTR), which can give rise to changes in mRNA stability and localization. However, little is known about the specific changes related to APA in stomach adenocarcinomas (STADs).
Methods: We integrated RNA sequencing data from The Cancer Genome Atlas and Genotype-Tissue Expression project to comprehensively analyze APA events in 289 cases of STAD.
Results: Our results showed that APA events were widespread in patients with STAD and were rich in genes related to known STAD pathways. The APA events result in the loss of tumor-suppressing micro-ribonucleic acid (miRNA) binding sites and increased heterogeneity in the length of the 3ʹ-UTR altered genes. Survival analysis revealed that specific subsets of 3ʹ-UTR-altered genes independently characterized a poor prognostic cohort among patients with STAD, thereby indicating the potential of APA as a new prognostic biomarker.
Conclusion: Our single-cancer analysis showed that by losing miRNA regulation, APA can become a driving factor for regulating the expression of oncogenic genes in STAD and promote its development. Our research revealed that APA events regulated STAD genes that were functionally related, thereby providing a new approach for gaining a better understanding of the progress of STADs and a means for identifying new drug targets as avenues of treatment.

Keywords: alternative polyadenylation, stomach adenocarcinoma, heterogeneity, 3′-UTR alerted genes


中文翻译：

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使用基因型-组织表达项目和癌症基因组图谱-胃腺癌谱鉴定胃腺癌中的替代多聚腺苷酸化

目的：选择性多聚腺苷酸化 (APA) 是一种常见机制，存在于大多数人类基因中，它决定了信使核糖核酸 (mRNA) 三个主要非翻译区 (3ʹ-UTR) 的长度，可引起 mRNA 稳定性和本土化。然而，关于胃腺癌 (STAD) 中与 APA 相关的具体变化知之甚少。
方法：我们整合癌症基因组图谱和基因型组织表达项目的 RNA 测序数据，全面分析 289 例 STAD 的 APA 事件。
结果：我们的研究结果表明，APA 事件在 STAD 患者中普遍存在，并且富含与已知 STAD 通路相关的基因。APA 事件导致肿瘤抑制微核糖核酸 (miRNA) 结合位点的丢失和 3'-UTR 改变基因长度的异质性增加。生存分析显示，特定的 3'-UTR 改变基因亚群独立地表征了 STAD 患者预后不良的队列，从而表明 APA 作为新的预后生物标志物的潜力。
结论：我们的单癌分析表明，通过失去 miRNA 调控，APA 可以成为调控 STAD 中致癌基因表达并促进其发展的驱动因素。我们的研究表明，APA 事件调节了功能相关的 STAD 基因，从而为更好地了解 STAD 的进展提供了一种新方法，并提供了一种将新药物靶点确定为治疗途径的方法。

关键词：替代多聚腺苷酸化，胃腺癌，异质性，3'-UTR 警报基因