Discovery and Validation of COL11A1 as a Therapeutic Target for Sorafenib Resistance in Lung Adenocarcinoma

Objective To investigate the expression characteristics, prognostic value, and role of COL11A1 in Sorafenib resistance in lung adenocarcinoma (LUAD). Methods The expression differences of COL11A1 in LUAD were analyzed based on The Cancer Genome Atlas (TCGA) database. Kaplan-Meier survival analysis was performed to evaluate prognostic value, and drug sensitivity analysis was conducted through the Genomics of Drug Sensitivity in Cancer (GDSC) database. Molecular mechanisms were explored using Weighted Gene Co-expression Network Analysis (WGCNA) and functional enrichment analysis. A549/Sorafenib-resistant cell line was established, and the effects of COL11A1 knockdown and overexpression on cell proliferation, apoptosis, migration, and invasion were examined. Results COL11A1 was significantly upregulated in LUAD, and patients with high expression showed poor prognosis. Drug sensitivity analysis revealed that COL11A1 was associated with sensitivity to multiple anticancer drugs, particularly Sorafenib resistance. Functional analysis indicated that COL11A1 primarily participated in extracellular matrix remodeling and collagen metabolic processes. Cell experiments confirmed that COL11A1 was highly expressed in resistant cells. Knockdown of COL11A1 reversed Sorafenib resistance, promoted cell apoptosis, and inhibited malignant phenotypes, while overexpression produced opposite effects. Conclusion COL11A1 mediates Sorafenib resistance by inhibiting tumor cell apoptosis and can serve as a potential target for treating drug resistance in LUAD.