Integrative Evaluation of the Clinical Significance Underlying Protein Arginine Methyltransferases in Hepatocellular Carcinoma

SIMPLE SUMMARY: Protein arginine methyltransferases (PRMTs) are a group of enzymes that play pivotal roles in post-translational modifications (PTMs) and are involved in the regulation of various cellular processes. Although PRMTs are recognized for their impact on the development and prognosis of various cancers, their specific involvement in hepatocellular carcinoma (HCC) remains relatively limited. In this study, we systematically evaluated the association between PRMTs and HCC prognosis, revealing their potential as prognostic biomarkers. We also highlighted the importance of PRMT1 and elucidated its role in HCC progression, especially in the context of T cell exhaustion (Tex). Our study underscores the prospective utility of PRMTs, particularly PRMT1, as promising prognostic indicators for HCC, as well as therapeutic targets for this malignancy. ABSTRACT: HCC is a major contributor to cancer-related mortality worldwide. Curative treatments are available for a minority of patients diagnosed at early stages; however, only a few multikinase inhibitors are available and are marginally effective in advanced cases, highlighting the need for novel therapeutic targets. One potential target is the protein arginine methyltransferase, which catalyzes various forms of arginine methylation and is often overexpressed in various cancers. However, the diverse expression patterns and clinical values of PRMTs in HCC remain unclear. In the present study, we evaluated the transcriptional expression of PRMTs in HCC cohorts using publicly available datasets. Our results revealed a significant association between PRMTs and prognosis in HCC patients with diverse clinical characteristics and backgrounds. This highlights the promising potential of PRMTs as prognostic biomarkers in patients with HCC. In particular, single-cell RNA (scRNA) sequencing analysis coupled with another human cohort study highlighted the pivotal role of PRMT1 in HCC progression, particularly in the context of Tex. Translating these findings into specific therapeutic decisions may address the unmet therapeutic needs of patients with HCC.