A system biology framework identifies immune associated prognostic biomarkers in colorectal cancer

Colorectal cancer (CRC) remains one of the leading causes of cancer related mortality worldwide. Although early detection and surgery improve survival, the prognosis of advanced disease is poor, and there is a critical need for biomarkers that integrate tumor intrinsic and immune microenvironment information. Here we applied an integrative systems biology workflow to colon adenocarcinoma data (۴۶۳ tumors and ۸۵ normal tissues) from The Cancer Genome Atlas using GEPIA۳ (FDR < ۰.۰۵, |log₂FC| ≥ ۲) to identify differentially expressed genes (DEGs). Gene ontology enrichment of ۹۹۲ DEGs highlighted extracellular matrix remodeling and innate immune pathways. Protein–protein and gene–gene interaction networks were constructed using STRING and GeneMANIA; degree and betweenness centrality were calculated in Cytoscape, and eight hub genes were defined as the intersection of the top thirty nodes in each network. Kaplan–Meier analysis using cSurvival revealed that two hubs, PRELP and TAGLN, significantly stratified overall survival (PRELP p = ۰.۰۱۴; TAGLN p = ۰.۰۳۹). Immune infiltration analysis with TISDB showed that high PRELP expression correlated positively with natural killer T cell abundance but negatively with activated CD۴⁺ T cells, whereas TAGLN correlated positively with natural killer and B cell abundance. Our results identify PRELP and TAGLN as immune associated prognostic biomarkers linking desmoplastic stroma to immunosuppression in CRC and propose them as potential targets for combination stromal depletion and immunotherapeutic strategies.

کلیدواژه ها:

colorectal cancer ، systems biology ، tumour microenvironment ، PRELP ، TAGLN