Gastroenterology and hepatology from bed to bench · 2025
Integrative systems biology identifies PRELP and TAGLN as prognostic biomarkers and immune modulators in colorectal cancer.
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Judaki Amir Ali, Aghemiri Mehran, Yousefli Zahra, Tavakkoli Sajjad, Taherkhani Amir, Nazari Elham, Arefi-Oskouie Afsaneh
Аннотация
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.
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.