TCGA and Bioinformatics Reveal the Molecular Network and Prognostic Implication of Laminin Beta 1 in Cholangiocarcinoma

This study investigates the expression, prognostic relevance, and molecular network of laminin subunit beta 1 (LAMB1) in cholangiocarcinoma (CCA) using TCGA data and bioinformatics tools. LAMB1 mRNA expression in CCA tissues was analyzed using the TCGA-CHOL dataset via GEPIA2, and protein expression data was obtained from The Human Protein Atlas (HPA). Survival analysis was performed using Kaplan–Meier plots and the log-rank test. Correlated genes were identified via UALCAN and analyzed for protein–protein interactions using STRING, followed by Gene Ontology (GO) and KEGG pathway enrichment. TCGA data showed significant upregulation of LAMB1 mRNA in CCA, and HPA images revealed stronger protein staining in CCA than in normal tissues. Although LAMB1 expression showed no significant association with overall survival (OS) or disease-free survival (DFS) in TCGA-CHOL alone, analysis of the combined CHOL and liver hepatocellular carcinoma (LIHC) datasets revealed that patients with high LAMB1 expression had significantly shorter OS and DFS. Among 250 LAMB1-correlated genes, STRING analysis identified 51 interacting partners, with GO and KEGG analyses highlighting enrichment in cell proliferation, DNA repair, and extracellular matrix (ECM)-related pathways. Notably, agrin (AGRN), collagen type IV alpha 5 chain (COL4A5), integrin alpha-2 (ITGA2), and nidogen 1 (NID1) emerged as network neighbors of LAMB1, with high AGRN and ITGA2 expression correlating with poor prognosis. These genes participate in ECM–integrin crosstalk and mechanotransduction signaling, processes that facilitate tumor progression and resistance to therapy. Together with our previous findings that LAMB1 promotes drug resistance and malignant phenotypes in CCA cells, these results reinforce LAMB1 as a central component of ECM-associated signaling networks and support its potential as a prognostic biomarker and therapeutic target.