Clinical value of MLH1-negative circulating tumor cells in lung cancer patients

Circulating tumor cells (CTCs) serve as valuable biomarkers. However, MutL homolog 1 (MLH1)-negative CTCs and their clinical significance in lung cancer are nearly unknown. Here, bioinformatic analysis of MLH1 expression and its clinical significance was conducted using the Oncomine, Ualcan, and Kaplan–Meier plotter websites. Size-based isolation and RNA in situ hybridization assays were used to identify CTCs and evaluate MLH1 and mesenchymal marker expression in CTCs. MLH1 was downregulated in lung cancer patients. Patients with lower MLH1 expression levels had worse prognoses. In a cohort of 32 randomly selected patients with lung cancer, the patients with poorer treatment responses had more MLH1-negative CTCs. The total CTCs, MLH1-negative CTCs and mesenchymal markers-expressing CTCs levels were negatively correlated with prognosis in the lung cancer patients. Our data showed the clinical significance of MLH1 expression in lung cancer tissues. The characterization and numeration of CTCs based on the expression of MLH1 and mesenchymal markers may be a convenient approach for predicting treatment response and prognosis in lung cancer.