Clinical Relevance of BACH1 Expression in Non-Small Cell Lung Cancer

BTB and CNC homolog 1 (BACH1) is a redox-sensitive transcription factor implicated in tumor progression, metabolic reprogramming, and therapy resistance in several cancers. However, its prognostic significance and role in therapy resistance in non-small cell lung cancer (NSCLC) remain unclear. BACH1 mRNA and protein expression were quantified in resected lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) tissues and matched non-tumor lung tissues and correlated with clinicopathological parameters, adjuvant chemotherapy status, and disease-free survival (DFS). Prognostic value was assessed using Kaplan-Meier and multivariate Cox regression analyses. In vitro, BACH1 expression was evaluated in seven NSCLC cell lines. Cisplatin sensitivity was determined by Annexin V apoptosis assays, and BACH1 silencing in H1975 and H1437 cells was used to assess effects on cisplatin response, migration, and colony formation. BACH1 expression was lower in LUAD and LUSC than in matched normal lung tissues but was higher in stage III tumors and in patients receiving adjuvant chemotherapy. In LUAD, high BACH1 expression was associated with shorter DFS, particularly in adjuvant chemotherapy. A significant interaction between BACH1 expression and chemotherapy suggested that the benefit of cisplatin-based treatment differed according to BACH1 status. Across seven NSCLC cell lines, BACH1 expression positively correlated with cisplatin resistance (r = 0.44, p = 0.035). BACH1 silencing enhanced cisplatin-induced cell death, suppressed migration, and clonogenic growth in H1975 and H1437 cells. Collectively, these findings identify BACH1 as a potential prognostic and predictive biomarker in chemotherapy-treated LUAD and support a functional role for BACH1 in mediating cisplatin resistance.