Predictive value of folate receptor-positive circulating tumor cells in postoperative progressive disease of non-small cell lung cancer patients

Abstract Background Postoperative recurrence and metastasis constitute critical obstacles for resected non-small cell lung cancer (NSCLC) patients, and reliable predictive biomarkers are still scarce. This study aimed to evaluate whether folate receptor-positive CTC (FR + CTC) predicts postoperative progressive disease (PD) in stage I–IIIA NSCLC and to explore noninvasive biomarkers for high-risk patients. Method We retrospectively enrolled stage I–IIIA NSCLC patients undergoing radical resection from 2018 to 2021. Perioperative blood samples were collected for FR + CTC detection. PD-related risk factors were analyzed to establish a postoperative prognostic model. Result In total, 171 NSCLC patients were enrolled. Stage III disease had higher preoperative FR⁺CTC positivity than stage I–II (69.39% vs. 52.46%, P = 0.043). Male gender, smoke, squamous histology and stage III correlated with elevated postoperative FR⁺CTC positivity (all P < 0.05). Among 152 patients for survival analysis, 36 developed 36‑month PD. Multivariate Cox confirmed postoperative FR⁺CTC positivity (HR = 2.25, P = 0.018) and stage III (HR = 3.43, P = 0.005) as independent PD predictors. FR⁺CTC conversion from preoperative negative to postoperative positive conferred the highest PD risk and shortened PFS. Conclusion Postoperative FR + CTC positive and TNM stage III were independent risk factors for 36 months PD in NSCLC patients after radical resection. Postoperative FR⁺CTC positivity correlated with shortened PFS and effectively predicted postoperative PD. Conversion from preoperative FR⁺CTC negativity to postoperative positivity conferred the highest progression risk. Perioperative FR⁺CTC detection and dynamic monitoring are promising liquid biopsy biomarkers for postoperative progression prediction.