Objective To explore the relationships of microRNA-125b (miR-125b), microRNA-142-5p (miR-142-5p) and microRNA-140-3p (miR-140-3p) with sensitivity to programmed death receptor-1 (PD-1) antibody therapy in patients with non-small cell lung cancer (NSCLC) and their clinical significance.

Methods A total of 219 NSCLC patients were selected and divided into sensitive group (n=92) and non-sensitive group (n=127) based on their sensitivity to PD-1 antibody therapy. Serum levels of miR-125b, miR-142-5p and miR-140-3p were compared between the two groups. A new combined predictor was constructed using miR-125b, miR-142-5p, and miR-140-3p through a Logistic regression model. The predictive performance was evaluated using the receiver operating characteristic (ROC) curve, and data were substituted into the equation forpredictive validation.

Results The serum level of miR-125b was higher in the non-sensitive group than that in the sensitive group, while the serum levels of miR-142-5pand miR-140-3p were lower in the non-sensitive group (P < 0.05). Logistic regression analysis showed that an increased level of miR-125b was an independent risk factor for sensitivity to PD-1 antibody therapy in NSCLC patients (P < 0.05), while increased levels of miR-142-5p and miR-140-3p were independent protective factors (P < 0.05). The optimal cut-off value for the combined predictor was 0.117, with a sensitivity of 90.22%, a specificity of 85.04%, and an accuracy of 87.21%. ROC curve analysis revealed that the area under the curve (AUC) for the combined predictor in predicting sensitivity to PD-1 antibody therapy was 0.928, which was significantly larger than the AUCs of 0.825, 0.817 and 0.772 for miR-125b, miR-142-5p and miR-140-3p, respectively (P < 0.05). A new equation was obtained by transforming the original Logistic regression equation, and data from three randomly selected patients were substituted into the equation for calculation, with predictive results being consistent with clinical reality.

Conclusion The miR-125b, miR-142-5p and miR-140-3p are all associated with sensitivity to PD-1 antibody therapy in NSCLC patients and can serve as biomarkers for predicting sensitivity to PD-1 antibody therapy. The combined predictor based on these three microRNAs can further enhance predictive value and provide more reliable reference information for clinical treatment decisions.