Integrating machine learning to construct aberrant alternative splicing event related classifiers to predict prognosis and immunotherapy response in patients with hepatocellular carcinoma

Front Pharmacol. 2022 Oct 3:13:1019988. doi: 10.3389/fphar.2022.1019988. eCollection 2022.

Abstract

Introduction: In hepatocellular carcinoma (HCC), alternative splicing (AS) is related to tumor invasion and progression. Methods: We used HCC data from a public database to identify AS subtypes by unsupervised clustering. Through feature analysis of different splicing subtypes and acquisition of the differential alternative splicing events (DASEs) combined with enrichment analysis, the differences in several subtypes were explored, cell function studies have also demonstrated that it plays an important role in HCC. Results: Finally, in keeping with the differences between these subtypes, DASEs identified survival-related AS times, and were used to construct risk proportional regression models. AS was found to be useful for the classification of HCC subtypes, which changed the activity of tumor-related pathways through differential splicing effects, affected the tumor microenvironment, and participated in immune reprogramming. Conclusion: In this study, we described the clinical and molecular characteristics providing a new approach for the personalized treatment of HCC patients.

Keywords: alternative splicing event; hepatocellular carcinoma; immune checkpoint molecules; machine learning; tumor microenvironment.