Multi-Omics and Clinical Data Analyses of Protein Arginine Methyltransferases in Pan-Cancer and Colorectal Cancer

Arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is a critical post-translational modification that modulates gene expression and signal transduction. Although the involvement of PRMTs in malignancy is increasingly recognized, a comprehensive pan-cancer synthesis of this family remains elusive. We sought to elucidate the multi-omic landscape of PRMTs and define their biological contributions to colorectal cancer (CRC) progression.

Using multi-omic data from TCGA and GTEx, we performed an integrative pan-cancer analysis of PRMT expression, genetic alterations, epigenetic modifications, and their associations with prognosis, genomic heterogeneity, stemness, the tumor microenvironment, and oncogenic pathways. After validating PRMT expression patterns across multiple independent CRC cohorts from the GEO database, PRMT1 was prioritized for further investigation. Its expression was assessed in a real-world CRC cohort using immunohistochemistry, while its oncogenic potential was scrutinized through in vitro proliferation assays.

PRMT family genes exhibit heterogeneous molecular profiles across cancers, which correlate significantly with genomic instability, stemness, immune infiltration, and oncogenic pathway activation. Clinical validation demonstrated that PRMT1 is markedly upregulated in CRC, where its overexpression correlates with larger tumor size, advanced T stage, and lymph node metastasis. Loss-of-function experiments demonstrated that PRMT1 is essential for maintaining CRC cell proliferation.

Our study highlights the multifaceted roles of PRMTs across the pan-cancer spectrum. By identifying PRMT1 as a key driver of CRC progression, this work provides a rationale for the development of PRMT-targeted therapies and personalized diagnostic biomarkers.