Zhang Jian, Goel Ajay, Zhu Lin
Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University, College Station, TX, United States.
Beckman Research Institute, City of Hope Comprehensive Cancer Center, Biomedical Research Center, Monrovia, CA, United States.
Front Oncol. 2021 Jun 8;11:640272. doi: 10.3389/fonc.2021.640272. eCollection 2021.
Alternative splicing (AS), e.g. the tandem alternative polyadenylation (TAPA), has emerged as major post-transcriptional modification events in human disease. However, the roles of the AS and TAPA in early-onset gastric cancer (EOGC) have not been revealed.
The global AS profiles of 80 EOGC patients were analyzed. The EOGC-specific AS events (ESASs) were identified in both the EOGC and adjacent non-tumor tissues. The functional enrichment analysis, Splicing network, Alternative Polyadenylation (APA) core factor network, and cell abundancy analysis were performed. Furthermore, the landscapes of the AS events in the varied subtypes of the EOGC patients were evaluated.
Overall, 66,075 AS events and 267 ESASs were identified in the EOGC. Furthermore, 4809 genes and 6152 gene isoforms were found to be aberrantly expressed in the EOGC. The Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analyses showed that the significant pathway alterations might exist in these AS events, genes, and gene isoforms. Moreover, the Protein-protein interaction (PPI) network analysis revealed that the UBC, NEK2, EPHB2, and DCTN1 genes were the hub genes in the AS events in the EOGC. The immune cell infiltration analysis indicated a correlation between the AS events and the cancer immune microenvironment. The distribution of the AS events in varied EOGC subtypes, protein phosphorylation and glycosylation was uneven.
The study highlighted the vital roles of the AS in the EOGC, including modulating the specific protein modification and reshaping the cancer immune microenvironment, and yielded new insights into the diagnosis of the EOGC as well as cancer treatment.
可变剪接（AS），如串联可变聚腺苷酸化（TAPA），已成为人类疾病中主要的转录后修饰事件。然而，AS和TAPA在早发性胃癌（EOGC）中的作用尚未明确。
分析了80例EOGC患者的整体AS图谱。在EOGC及其相邻的非肿瘤组织中鉴定出EOGC特异性AS事件（ESASs）。进行了功能富集分析、剪接网络、可变聚腺苷酸化（APA）核心因子网络和细胞丰度分析。此外，还评估了EOGC患者不同亚型中AS事件的情况。
总体而言，在EOGC中鉴定出66075个AS事件和267个ESASs。此外，发现4809个基因和6152个基因异构体在EOGC中异常表达。基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析表明，这些AS事件、基因和基因异构体中可能存在显著的通路改变。此外，蛋白质-蛋白质相互作用（PPI）网络分析显示，UBC、NEK2、EPHB2和DCTN1基因是EOGC中AS事件的枢纽基因。免疫细胞浸润分析表明AS事件与癌症免疫微环境之间存在相关性。AS事件在不同EOGC亚型中的分布、蛋白质磷酸化和糖基化是不均匀的。
该研究强调了AS在EOGC中的重要作用，包括调节特定蛋白质修饰和重塑癌症免疫微环境，并为EOGC的诊断和癌症治疗提供了新的见解。
