Cancer cells with stem-like properties are major contributors to limited therapeutic efficacy and poor five-year survival rates. The identification of stemness-associated biomarkers is critical for improving diagnosis, prognosis evaluation, and treatment selection in lung cancer patients. Here, we employed weighted gene co-expression network analysis (WGCNA) and Venn analysis to identify BUB1 as a key stemness-associated gene. Our results revealed a significantly elevated mRNA stemness index (mRNAsi) in lung cancer tissues, with BUB1 as a hub gene in stemness-related modules. Clinically, BUB1 expression was markedly upregulated in lung cancer and demonstrated excellent diagnostic value, showing high area under the curve (AUC), sensitivity and specificity in ROC analysis. Elevated BUB1 expression strongly predicted poorer survival outcomes in LUAD patients. Mechanistically, BUB1 knockdown suppressed stem-like features, reducing tumor sphere formation and downregulating stemness markers through inactivation of the IL-17 signaling pathway. Molecular docking identified three potential BUB1-targeting drugs (quercetin, cryptolepine, etoposide) with stable binding conformations. Collectively, our fingdings established BUB1 as a diagnostic biomarker for lung cancer, an independent prognostic indicator for LUAD, and a promising therapeutic target, with its inhibition potentially overcoming CSCs-driven treatment resistance.
Liu et al. (2026) studied this question.