PDF(Pubmed)
Abstract：
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.
摘要：
已在各种癌症中检测到由关键剪接因子基因（SFG）的体细胞突变引起的剪接异常。因此，深入研究剪接因子基因突变对泛癌症的影响是有意义的。这项研究调查了剪接因子基因突变与临床特征的关联。肿瘤进展表型，基因组完整性，抗肿瘤免疫反应，和来自TCGA数据库的12种常见癌症类型的免疫治疗反应。与SFG野生型癌症相比，SFG突变的癌症显示较差的生存预后，更高的肿瘤突变负荷和非整倍性水平，免疫抑制特征的较高表达，和更高水平的肿瘤干性，扩散潜力，和肿瘤内异质性(ITH)。然而,在6个癌症队列中,剪接因子基因突变的癌症对免疫检查点抑制剂的应答率高于剪接因子基因-野生型癌症.单细胞数据分析证实剪接因子基因突变与肿瘤干性增强有关,增殖能力,PD-L1表达，肿瘤内异质性，和非整倍体水平。我们的数据表明，关键剪接因子基因的突变与不利的临床结果和疾病进展有关。基因组不稳定性，抗肿瘤免疫抑制，和增强泛癌症的免疫疗法反应。因此，剪接因子基因突变是一种不良预后因素,也是癌症免疫治疗反应的阳性标志物.
