Profiles of prognostic alternative splicing signature in hepatocellular carcinoma

Cancer Medicine

Xiaoran Duan¹  Chaojun Liu¹  Huicun Cao²  Jian Liu²  Fangming Wu²  Hui Li²  Qifeng Chen³  Wang Li³  Jinlong Hu⁴ 

[1] Biotherapy Center the First Affiliated Hospital of Zhengzhou University Zhengzhou China;Department of Comprehensive Intervention Henan Provincial People's Hospital Zhengzhou China;Department of Medical Imaging and Interventional Radiology Sun Yat‐sen University Cancer Center Guangzhou China;Department of Oncology Henan Provincial People's Hospital Zhengzhou China;

关键词: alternative splicing;    hepatocellular carcinoma;    prognosis;    TCGA;    survival;   

DOI  :  10.1002/cam4.2875

来源: DOAJ

【 摘 要 】

Abstract Previous studies have demonstrated the role of abnormal alternative splicing (AS) in tumor progression. This study examines the prognostic index (PI) of alternative splices (ASs) in patients with hepatocellular carcinoma (HCC). The clinical features and splicing events of patients with HCC were downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed AS (DEAS) were compared between HCC and adjacent normal samples. Univariate Cox regression analysis was used to determine changes in DEAS associated with overall survival (OS). A PI was generated from OS‐associated DEASs using Kaplan‐Meier curves, receiver operating characteristic (ROC) curves, multivariate Cox regression, and cluster analysis. Then, the correlation between DEASs and splicing factors was assessed, followed by functional and pathway enrichment analysis. We identified 34 163 ASs of 8985 genes in HCC, and 153 OS‐ASs were identified using univariate Cox regression analysis. Low‐ and high‐PI groups were determined based on the median “PI‐ALL” value according to significantly different survival (P = 2.2e − 16). The ROC curve of all PI (PI‐ALL) had an area under the curve (AUC) of 0.993 for survival status in patients with HCC. A potential regulatory network associated with prognosis of patients with HCC was established. Enrichment analysis also resulted in the identification of several pathways potentially associated with carcinogenesis and progression of HCC. Four clusters were identified that were associated with clinical features and prognosis. Our study generated comprehensive profiles of ASs in HCC. The interaction network and functional connections were used to elucidate the underlying mechanisms of AS in HCC.

【 授权许可】

Unknown