Preoperative Folate Receptor-Positive Circulating Tumor Cells Are Associated With Occult Peritoneal Metastasis and Early Recurrence in Gastric Cancer Patients: A Prospective Cohort Study

BackgroundThe aim of this study is to explore the clinical feasibility of detecting folate receptor-positive circulating tumor cells (FR+ CTCs) for predicting peritoneal metastasis and short-term outcome in gastric cancer patients. MethodsThis is a prospective, single-center, observational study. We applied ligand-targeted enzyme-linked polymerization method to detect preoperative FR+ CTC levels in peripheral blood. We evaluated the diagnostic value of FR+ CTCs and other biomarkers in predicting peritoneal metastasis. Prognostic factors for recurrence-free survival (RFS) were investigated in univariate and multivariate analyses. ResultsA total of 132 patients with gastric cancer and 9 patients with benign disease were recruited. Gastric cancer patients had a significantly higher CTC level compared to that of patients with benign disease (p < 0.01). Combined model including CTC level and other biomarkers presented high sensitivity (100%) and moderate specificity (59.3%) in predicting peritoneal metastasis. Univariate analysis revealed that decreased serum prealbumin, decreased peripheral lymphocyte count, FR+ CTCs, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and lymph node metastasis were significantly associated with shorter RFS. FR+ CTC level [>= 12.6 folate units (FU)/3 ml, hazard ratio (HR) = 6.957, p = 0.005] and CA19-9 (>34 ng/ml, HR = 3.855, p = 0.037) were independent prognostic factors in multivariate analysis. ConclusionsOur findings for the first time suggested the diagnostic value of preoperative CTC levels in predicting peritoneal metastasis in gastric cancer. Moreover, the FR+ CTC level could be a novel and promising prognostic factor for the recurrence of gastric cancer in patients who underwent surgery.