The Role of SRMS in Colorectal Cancer by Bioinformatics Analysis

Abstract Background:Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (SRMS) is a non-receptor tyrosine kinase that has been found to be overexpressed in various tumors. Therefore, it may be an important carcinogenic factor whose role in colorectal cancer (CRC) has not been established. Methods: We evaluated the expression patterns of SRMS in CRC using GEPIA, Oncomine and HPA datasets while the association between SRMS and clinicopathological features was analyzed using a UALCAN dataset. LinkedOmics was used to determine co-expression and functional networks associated with SRMS. Besides, we used TISIDB to assess the correlation between SRMS and immune signatures, including tumor-infiltrating immune cells and immunomodulators. Lastly, protein-protein interaction network establishment and pathway enrichment analysis of the SRMS-associated 33 immunomodulators and 191 immune cell marker genes were performed using the STRING portal. Results: Compared to normal colorectal tissues, SRMS was found to be upregulated in CRC tissues, and was correlated with higher pathological stages and nodal metastasis status. Functional network analysis suggested that SRMS regulates intermediate filament-based processes, protein autophosphorylation, translational initiation and elongation signaling through pathways involving ribosomes, proteasomes, oxidative phosphorylation, and DNA replication. In addition, SRMS expression was correlated with infiltrating levels of CD4+ T cells, CD56dim, MEM B, Neutrophils, Th2, Th17, and Act DC. Pathway enrichment analysis of SRMS-associated 33 immunomodulators and 191 immune cell marker genes indicated that they are involved multiple cancer-related pathways. Conclusions: SRMS is a promising prognostic biomarker and a potential therapeutic target for CRC patients. In particular, SRMS regulates CRC progression by modulating chemokines, IL-17, intestinal immune networks for IgA production, and cytokine-cytokine receptor interaction signaling pathways among others. However, more studies are needed to validate these findings.