Prognostic Significance of Alternative Splicing Genes in Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma

Xiaoyu Wang; Weichun Tang; Yilin Lu; Jun You; Yun Han; Yanli Zheng

doi:10.2147/IJGM.S335475

Prognostic Significance of Alternative Splicing Genes in Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma

Int J Gen Med. 2021 Nov 9:14:7933-7949. doi: 10.2147/IJGM.S335475. eCollection 2021.

Authors

Xiaoyu Wang^#¹, Weichun Tang^#¹, Yilin Lu¹, Jun You¹, Yun Han¹, Yanli Zheng¹

Affiliation

¹ Department of Obstetrics and Gynecology, Nantong First People's Hospital, Nantong, Jiangsu, 226001, People's Republic of China.

^# Contributed equally.

Abstract

Background: Alternative splicing (AS) acts on many tumors and its relationship with cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) needs to be researched.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: AS; CESC; TCGA; alternative splicing; cervical squamous cell carcinoma and endocervical adenocarcinoma; prognosis.

Grants and funding

This research was supported by Maternal and Child Health Research Project of Jiangsu Provincial Health Commission (F201836), Nantong Municipal Health Commission Youth Project A (QA202004) and the Research project of Nantong health Committee project B (MB2020003).