Identification of prognostic alternative splicing events related to the immune microenvironment of hepatocellular carcinoma

Molecular Medicine

Shanshan Yu¹  Lingyi Cai²  Leying Zhuo³  Chuan Liu⁴  Ruihong Gu⁵  Luya Cai⁶ 

[1] Department of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China;Department of Hematology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China;Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Southern White Elephant Town, Ouhai, 325000, Wenzhou, Zhejiang, People’s Republic of China;Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China;Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China;Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China;

关键词: Hepatocellular carcinoma;    Alternative splicing;    Prognosis;    Carcinogenesis;    Immune microenvironment;   

DOI  :  10.1186/s10020-021-00294-3

来源: Springer

【 摘 要 】

BackgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, and its 5-year survival rate is less than 20%, despite various treatments being available. Increasing evidence indicates that alternative splicing (AS) plays a nonnegligible role in the formation and development of the tumor microenvironment (TME). However, the comprehensive analysis of the impact on prognostic AS events on immune-related perspectives in HCC is lacking but urgently needed.MethodsThe transcriptional data and clinical information of HCC patients were downloaded from TCGA (The Cancer Genome Atlas) database for calculating immune and stromal scores by ESTIMATE algorithm. We then divided patients into high/low score groups and explored their prognostic significance using Kaplan–Meier curves. Based on stromal and immune scores, differentially expressed AS events (DEASs) were screened and evaluated with functional enrichment analysis. Additionally, a risk score model was established by applying univariate and multivariate Cox regression analyses. Finally, gene set variation analysis (GSVA) was adopted to explore differences in biological behaviors between the high- and low-risk subgroups.ResultsA total of 370 HCC patients with complete and qualified corresponding data were included in the subsequent analysis. According to the results of ESTIMATE analysis, we observed that the high immune/stromal score group had a longer survival probability, which was significantly correlated with prognosis in HCC patients. In addition, 467 stromal/immune score-related DEASs were identified, and enrichment analysis revealed that DEASs were significantly enriched in pathways related to HCC tumorigenesis and the immune microenvironment. More importantly, the final prognostic signature containing 16 DEASs showed powerful predictive ability. Finally, GSVA demonstrated that activation of carcinogenic pathways and immune-related pathways in the high-risk group may lead to poor prognosis.ConclusionsCollectively, these outcomes revealed prognostic AS events related to carcinogenesis and the immune microenvironment, which may yield new directions for HCC immunotherapy.

【 授权许可】

CC BY