Integrative systems biology identifies PRELP and TAGLN as prognostic biomarkers and immune modulators in colorectal cancer.

AIM: To identify prognostic biomarkers in colorectal cancer (CRC) using an integrative systems biology approach combining transcriptomics, network topology, and immune profiling.

BACKGROUND

Advanced CRC prognosis remains poor due to a lack of biomarkers capturing tumor-immune interactions. Current single-gene markers often overlook the network-based nature of tumorigenesis.

METHODS

We analyzed TCGA-COAD data (n = 463 tumor, n = 85 normal) using GEPIA3 with thresholds of |log_2FC| > 2 and adjusted p. value < 0.05. Protein-protein and gene-gene interaction networks were constructed via STRING (confidence > 0.4) and GeneMANIA. Hub genes were prioritized by intersecting degree and betweenness centrality using Cytoscape. Prognosis was assessed using cSurvival (Kaplan-Meier) and immune correlations via TISDB. Protein expression was verified in the Human Protein Atlas and external validation was performed to justify accuracy of candidate biomarkers.

RESULTS

Analysis revealed 992 DEGs (498 up-regulated and 494 down-regulated) enriched in extracellular matrix organization and innate immune pathways. Eight dual hub genes were identified; PRELP and TAGLN significantly predicted overall survival. High PRELP (p= 0.014) and TAGLN (p = 0.039) expression predicted poor prognosis. Both positively correlated with innate immune cells (NKT/NK cells) but negatively with activated CD4+ T cells, suggesting immune exclusion.

CONCLUSION

PRELP and TAGLN are novel dual prognostic biomarkers linking stromal remodeling to immunosuppression in CRC. High tissue expression serves as a marker of desmoplastic stroma and poor survival, emphasizing context-dependent biomarker evaluation.