SETD8 is a prognostic biomarker that contributes to stem-like cell properties in non-small cell lung cancer

SETD8 is a lysine methyltransferase containing an SET domain and has been reported to regulate various biological processes, including carcinogenesis. However, its prognostic value and mechanisms of action in non-small cell lung cancer (NSCLC) have not been extensively studied. Here, we assessed SETD8 expression and its relationship with clinicopathological parameters, cancer stemness proteins, and cell cycle-regulating proteins in NSCLC. SETD8 expression in NSCLC tissues was correlated with primary tumor stage, lymph node metastases, and clinical stage. Moreover, SETD8 was an independent predictor of poor overall survival in NSCLC. A Cox regression analysis showed that SETD8 was a potential biomarker of unfavorable clinical outcomes in patients with NSCLC. SETD8 overexpression was associated with cancer stemness-related genes and cell cycle-related genes in NSCLC tissue samples. SETD8 silencing significantly reduced the expression of cancer stemness-associated genes (CD44, LGR5, and SOX2) and inhibited NSCLC cell proliferation, spheroid formation, invasion, and migration. Our findings demonstrate that SETD8 may be a novel cancer stemness-associated protein and a potential prognostic biomarker in NSCLC.