Wang Xiaoyu, Tang Weichun, Lu Yilin, You Jun, Han Yun, Zheng Yanli
Department of Obstetrics and Gynecology, Nantong First People's Hospital, Nantong, Jiangsu, 226001, People's Republic of China.
Int J Gen Med. 2021 Nov 9;14:7933-7949. doi: 10.2147/IJGM.S335475. eCollection 2021.
Alternative splicing (AS) acts on many tumors and its relationship with cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) needs to be researched.
RNA sequencing data and clinical information of CESC cohorts were obtained from the Cancer Genome Atlas (TCGA) and SpliceSeq was used to analyze the splicing profile of mRNA in CESC. UpSetR displayed the intersections among AS events and univariate analysis chose survival-associated AS and splicing factor (SF) genes. Functional analysis was operated on Enrichr, STRING database and MCODE analysis were used to evaluate protein-protein interaction (PPI) information. LASSO and multivariate analysis constructed prognostic model and risk analysis of tumor infiltrating immune cells was also conducted.
A total of 402 AS-generated genes were found to be associated with CESC prognosis. Functional analysis showed that Golgi to lysosome transport was enriched. PPI network suggested that UBA52 was most functional. Dendritic cells activated, dendritic cells resting, macrophages M0, mast cells resting, T cells CD4 memory activated and T cells CD8 were most correlative with the risk score.
SFs and AS events can directly or indirectly affect the prognosis of CESC patients and this study identified SNRPA and CELF2 as two CESC-engaged SFs.
可变剪接(AS)作用于多种肿瘤,其与宫颈鳞状细胞癌和宫颈内膜腺癌(CESC)的关系有待研究。
从癌症基因组图谱(TCGA)获取CESC队列的RNA测序数据和临床信息,并用SpliceSeq分析CESC中mRNA的剪接图谱。UpSetR展示AS事件之间的交集,单变量分析选择与生存相关的AS和剪接因子(SF)基因。在Enrichr上进行功能分析,使用STRING数据库和MCODE分析评估蛋白质-蛋白质相互作用(PPI)信息。LASSO和多变量分析构建预后模型,并对肿瘤浸润免疫细胞进行风险分析。
共发现402个由AS产生的基因与CESC预后相关。功能分析表明高尔基体到溶酶体的转运得到富集。PPI网络表明UBA52功能最强。树突状细胞激活、静息树突状细胞、M0巨噬细胞、静息肥大细胞、CD4记忆激活T细胞和CD8 T细胞与风险评分相关性最高。
SF和AS事件可直接或间接影响CESC患者的预后,本研究确定SNRPA和CELF2为两个参与CESC的SF。