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Published on: July 22, 2020
The possible role of SRMS in colorectal cancer by bioinformatics analysis
Jie Zhang1, Weidong Liu1, Sisi Feng2
1Department of Clinical Laboratory, Xiangya Hospital, Central South University, 87 Xiangya Road, Kaifu District, Changsha, 410008, China.
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. However, the role of SRMS in colorectal cancer (CRC) has not been well established.
Methods:
We evaluated the expression levels of SRMS in CRC using GEPIA, Oncomine, and HPA datasets. Survival information and gene expression data of CRC were obtained from The Cancer Genome Atlas (TCGA). Then, the association between SRMS and clinicopathological features was analyzed using 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 (PPI) was established and the function enrichment analysis of the SRMS-associated immunomodulators and immune cell marker genes were performed using the STRING portal.
Results:
Compared to normal colorectal tissues, SRMS was found to be overexpressed in CRC tissues, which was correlated with a poor prognosis. In colon adenocarcinoma (COAD), the expression levels of SRMS are significantly correlated with 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. The gene ontology (GO) analysis of SRMS-associated immunomodulators and immune cell marker genes showed that they were mainly enriched in the immune microenvironment molecule-related signals. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of these genes indicated that they are involved in multiple cancer-related pathways.
Conclusions:
SRMS is a promising prognostic biomarker and potential therapeutic target for CRC patients. In particular, SRMS regulates CRC progression by modulating cytokine-cytokine receptor interaction, chemokines, IL-17, and intestinal immune networks for IgA production signaling pathways among others. However, more studies are needed to validate these findings.
Insights
Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (SRMS) is overexpressed in colorectal cancer (CRC), correlating with poor prognosis. SRMS influences tumor progression and immune cell infiltration, suggesting its potential as a prognostic biomarker and therapeutic target in CRC.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (SRMS) is a non-receptor tyrosine kinase.
- SRMS overexpression is observed in various tumors, but its role in colorectal cancer (CRC) remains unclear.
Purpose of the Study:
- To investigate the expression levels and prognostic significance of SRMS in colorectal cancer (CRC).
- To explore the association between SRMS and clinicopathological features, immune cell infiltration, and related signaling pathways in CRC.
Main Methods:
- Utilized public datasets (GEPIA, Oncomine, HPA, TCGA, UALCAN) to analyze SRMS expression and its correlation with clinicopathological features and survival in CRC.
- Employed LinkedOmics and TISIDB for co-expression, functional network, and immune signature analyses.
- Constructed protein-protein interaction networks and performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses.
Main Results:
- SRMS was significantly overexpressed in CRC tissues compared to normal tissues, correlating with poorer prognosis.
- SRMS expression was associated with pathological stages and nodal metastasis in colon adenocarcinoma (COAD).
- SRMS regulates pathways involved in intermediate filament, protein autophosphorylation, and translation, and correlates with the infiltration of various immune cells (e.g., CD4+ T cells, Neutrophils, Th17).
- GO and KEGG analyses revealed enrichment in immune microenvironment and cancer-related pathways.
Conclusions:
- SRMS serves as a potential prognostic biomarker and therapeutic target for CRC.
- SRMS modulates CRC progression through cytokine-cytokine receptor interactions, chemokines, IL-17, and intestinal immune networks.
- Further research is warranted to validate these findings and explore therapeutic strategies targeting SRMS.
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