Comprehensive Molecular Analysis Identified an SRSF Family-Based Score for Prognosis and Therapy Efficiency Prediction in Hepatocellular Carcinoma

SIMPLE SUMMARY: Hepatocellular carcinoma (HCC) remains one of the most common malignancies worldwide. Despite significant progress in the comprehensive management of HCC, continued efforts are still necessary to identify prognostic assessment approaches for patient-specific survival so that more appropriate treatment and management regimens can be proposed for different HCC subpopulations. Here, we comprehensively exploited the expression characteristics of 12 SRSF family members across multiple datasets. We further identified an SRSF score consisting of 18 SRSF-related genes which were associated with overall survival and drug sensitivity in HCC. Moreover, the predictive power of the SRSF score was validated in independent HCC cohorts and different HCC subgroups. We further explored the effect of SRSF11 expression on HCC cell proliferation and drug sensitivity. Overall, our study provides a novel predictive model to assess the prognosis and drug sensitivity of HCC. ABSTRACT: The serine/arginine-rich splicing factors (SRSF)-mediated alternative splicing plays an essential role in the occurrence and progression of hepatocellular carcinoma (HCC). However, the SRSF-based signature that can predict the prognosis and therapy efficiency is yet to be investigated in HCC. Here, we comprehensively assessed the landscape and prognostic significance of the SRSF family genes in HCC. Then, we screened the SRSF family-related genes for signature construction and explored their biological characteristics. We further established an SRSF score consisting of 18 SRSF-associated genes and evaluated its correlation with prognosis and drug sensitivity in HCC. The predictive power of the SRSF score was validated in independent HCC cohorts and different HCC subgroups. Moreover, we further investigated that knockdown of SRSF11, a pivotal gene in the SRSF score, inhibited CDK1-dependent proliferation and enhanced the drug sensitivity of HCC cells. Overall, our study identified a novel SRSF family-based predictive model, and we demonstrated that SRSF11 is a promising therapeutic target for HCC, which enhances our understanding of the SRSF family genes and provides valuable insights into the clinical treatment and molecular mechanisms of HCC.