WDR35 Is Associated with Chemosensitivity and Prognosis in Lung Adenocarcinoma

Background: This study investigated the expression characteristics of WD repeat domain 35 (WDR35) in lung adenocarcinoma (LUAD) and its association with chemotherapy sensitivity and prognosis. Methods: Differentially expressed genes were analyzed in combination with Random Forest and Support Vector Machine algorithms to identify key genes associated with chemotherapy sensitivity. The expression differences of the core gene at both transcriptomic and proteomic levels were then experimentally validated using real-world LUAD samples. Drug sensitivity analysis was conducted using the Genomics of Drug Sensitivity in Cancer database to evaluate the correlation between the core gene and the IC₅₀ values of various chemotherapeutic agents. Gene Set Enrichment Analysis (GSEA) was used to explore the potential mechanisms involved. Finally, Kaplan-Meier survival analysis and stratified analysis by tumor stage and lymph node status were performed to assess the prognostic value of the core gene. Results: WDR35 as a core gene associated with chemotherapy sensitivity and highly expressed in normal lung tissue compared with tumor tissue, which was further validated at both the qPCR and proteomic levels. Clinical correlation analysis indicated that WDR35 expression is significantly associated with tumor size, lymph node metastasis, and tumor stage. Further analysis revealed that patients with high WDR35 expression were more likely to achieve partial or complete response to initial chemotherapy. Drug sensitivity prediction analysis demonstrated that high WDR35 expression was significantly correlated with increased sensitivity to various anticancer drugs. GSEA pathway enrichment analysis suggested that WDR35 may enhance chemotherapy sensitivity by regulating stress response and metabolic pathways. Survival analysis indicated that high WDR35 expression was associated with better overall survival and disease-specific survival. Conclusions: Our study reveals that WDR35 is closely associated with chemotherapy sensitivity and prognosis in lung adenocarcinoma.