Research Paper Volume 13, Issue 19 pp 23149—23168
Comprehensive analysis of aberrant alternative splicing related to carcinogenesis and prognosis of papillary thyroid cancer
- 1 Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
- 2 Department of General Surgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan, China
- 3 Department of Otolaryngology Head and Neck Surgery, General Hospital of Western Theater Command, Chengdu 610083, Sichuan, China
- 4 Laboratory of Tumor Targeted and Immune Therapy, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
- 5 Hearing Center/Hearing and Speech Laboratory, Department of Otorhinolaryngology Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
- 6 Department of General Surgery, Mianzhu Hospital of West China Hospital, Sichuan University, Mianzhu 618200, Sichuan, China
- 7 Department of Hepatopancreatobiliary Surgery, Meishan Hospital of West China Hospital, Sichuan University, Meishan City People’s Hospital, Meishan 610020, Sichuan, China
Received: February 3, 2021 Accepted: May 13, 2021 Published: October 8, 2021
https://doi.org/10.18632/aging.203608How to Cite
Copyright: © 2021 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
As a key mechanism, alternative splicing (AS) plays a role in the cancer initiation and development. However, in papillary thyroid cancer (PTC), data for the comprehensive AS event profile and its clinical implications are lacking. Herein, a genome-wide AS event profiling using RNA-Seq data and its correlation with matched clinical information was performed using a 389 PTC patient cohort from the project of The Cancer Genome Atlas (TCGA). We identified 1,925 cancer-associated AS events (CASEs) by comparing paired tumors and neighboring healthy tissues. Parent genes with CASEs remarkably enriched in the pathways were linked with carcinogenesis, such as P53, KRAS, IL6-JAK-STAT3, apoptosis, and MYC signaling. The regulatory networks of AS implied an obvious correlation between the expression of splicing factor and CASE. We identified eight CASEs as predictors for overall survival (OS) and disease-free survival (DFS). The established risk score model based on DFS-associated CASEs successfully predicted the prognosis of PTC patients. From the unsupervised clustering analysis results, it is found that different clusters based on AS correlated with prognosis, molecular features, and immune characteristics. Taken together, the comprehensive genome-wide AS landscape analysis in PTC showed new AS events linked with tumorigenesis and prognosis, which provide new insights for clinical monitoring and therapy for PTC.
Abbreviations
PTC: papillary thyroid cancer; AS: alternative splicing; TCGA: The Cancer Genome Atlas; CASEs: Cancer-associated AS events; SFs: splicing factors. TME: tumor microenvironment; THCA: thyroid cancer; PSI: Percent Spliced In; NK: natural killer; TMB: tumor mutational burden; KEGG: Kyoto Encyclopedia of Genes and Genomes; GO: Gene Ontology; GSEA: Gene Set Enrichment Analysis; HRs: Hazard ratios; OS: overall survival; DFS: disease-free survival; ROC: receiver operating characteristic; ES: exon skipping; AP: alternate promoter; AT: alternate terminator; AD: alternate donor; AA: alternate acceptor; ME: exclusive exons; RI: retained intron; PPI: protein-protein interaction; LASSO: least absolute shrinkage and selection operator.