■结肠腺癌(COAD)是全球癌症死亡的主要原因之一。选择性聚腺苷酸化(APA)与mRNA的3'-UTR的变异性有关。然而,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(n=7692)收集APA数据。使用PDUI值评估APA事件,并通过LASSOCox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调控基因的免疫调节网络。
■共发现95个APA事件影响COAD结果。其中,通过LASSOCox回归筛选39个基因作为特征性预后APA事件,以构建COAD预后标签。分析结果表明,高签名评分与不良预后相关,并与多种免疫细胞显着相关,包括NK和Th1、2和17细胞。进一步分析表明,APA调节因子主要在COAD的预后中起作用。基于以上结果,我们构建了APA调节基因-APA基因-免疫细胞的免疫调节网络。
■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,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。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.