VDAC1 as prognostic marker and therapeutic target in lung adenocarcinoma: a study integrating bioinformatics and experimental validation

Background: Research on the expression and molecular mechanisms of voltage-dependent anion channels (VDACs) in lung adenocarcinoma (LUAD) remains limited.

Materials and methods: Multiple datasets were utilized to analyze VDACs expression in LUAD and investigate the clinical significance of VDACs-associated genes and signaling pathways. The database analysis results were further validated through cellular and animal experiments.

Results: The expression levels of VDAC1 and VDAC2 increase with advancing tumor stage. Subsequent survival analysis revealed that elevated mRNA expression of VDAC1 (HR = 1.6, log-rank P = 0.0015), VDAC2 (HR = 1.5, log-rank P = 0.0088), and VDAC3 (HR = 1.7, log-rank P = 0.0026) was significantly associated with shorter overall survival in LUAD patients. The VDACs-based prognostic signature holds significant value for risk stratification, with VDAC1 demonstrating the poorest prognostic impact. We demonstrated that both in vitro and in vivo experiments consistently showed that the combination of trametinib with VBIT-12 markedly suppresses tumor growth.

Conclusion: This study integrates bioinformatic insights with experimental validation to clarify the clinical significance and therapeutic potential of VDACs in LUAD, providing a valuable foundation for prognosis assessment and targeted therapy development.

Bioinformatics; Diagnosis; Lung adenocarcinoma; Prognosis; Targeted therapy; VDAC.