The mutation in splicing factor genes correlates with unfavorable prognosis, genomic instability, anti-tumor immunosuppression and increased immunotherapy response in pan-cancer

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Jiangti Luo¹  Canping Chen¹  Xiaosheng Wang¹  Zhixian Liu² 

[1] Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China;Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China;Big Data Research Institute, China Pharmaceutical University, Nanjing, China;Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China;

关键词: somatic mutations;    splicing factor genes;    pan-cancer;    cancer prognosis;    anti-tumor immune responses;    cancer immunotherapy;    genomic instability;   

DOI  :  10.3389/fcell.2022.1045130

 received in 2022-09-15, accepted in 2022-12-21,  发布年份 2023

来源: Frontiers

【 摘 要 】

Splicing abnormality resulting from somatic mutations in key splicing factor genes (SFG) has been detected in various cancers. Hence, an in-depth study of splicing factor genes mutations’ impact on pan-cancer is meaningful. This study investigated associations of splicing factor genes mutations with clinical features, tumor progression phenotypes, genomic integrity, anti-tumor immune responses, and immunotherapy response in 12 common cancer types from the TCGA database. Compared to SFG-wildtype cancers, SFG-mutated cancers displayed worse survival prognosis, higher tumor mutation burden and aneuploidy levels, higher expression of immunosuppressive signatures, and higher levels of tumor stemness, proliferation potential, and intratumor heterogeneity (ITH). However, splicing factor genes-mutated cancers showed higher response rates to immune checkpoint inhibitors than splicing factor genes-wildtype cancers in six cancer cohorts. Single-cell data analysis confirmed that splicing factor genes mutations were associated with increased tumor stemness, proliferation capacity, PD-L1 expression, intratumor heterogeneity, and aneuploidy levels. Our data suggest that the mutation in key splicing factor genes correlates with unfavorable clinical outcomes and disease progression, genomic instability, anti-tumor immunosuppression, and increased immunotherapy response in pan-cancer. Thus, the splicing factor genes mutation is an adverse prognostic factor and a positive marker for immunotherapy response in cancer.

【 授权许可】

Unknown   
Copyright © 2023 Luo, Chen, Liu and Wang.