Evaluation of cell surface vimentin positive circulating tumor cells as a prognostic biomarker for stage III/IV colorectal cancer

Abstract

Currently, little is known about the phenotypes of circulating tumor cells (CTCs), particularly epithelial and mesenchymal phenotypes, and their impact on the prognosis of colorectal cancer (CRC) patients. This study aims to investigate the CTC phenotypes and their prognostic implications in stage III/IV CRC. Patients who were diagnosed with CRC and underwent CTC detection at two hospitals were included. CTCs were detected using a mesenchymal CTC kit, and the clinical and pathological characteristics of CTCs were compared with those of cell surface vimentin-positive CTCs (CSV-CTCs). Disease-free survival (DFS) was assessed and used as an indicator of CTC phenotype-related prognosis. Univariate and multivariate Cox regression analyses were made to identify risk factors, and nomogram models were employed for prognostic prediction. A total of 82 patients were enrolled, with a CTC detection rate of 86.6%. Among the detected CTCs, 60% were CSV-CTCs. The CSV-CTC count showed a positive correlation with the T-stage, the M-stage, and the location of the primary tumor (P = 0.01, P = 0.014, and P = 0.01, respectively). Kaplan–Meier survival analysis revealed that CSV-CTCs were associated with worse DFS in patients receiving first-line oxaliplatin chemotherapy (hazard ratio (HR) = 3.78, 95% CI 1.55–9.26, p = 0.04). When the cut-off value of the CSV-CTC count was 3, the optimal prognostic prediction was achieved. Compound models considering CSV-CTCs, TNM staging, the site of the primary tumor and the Ras gene status yielded the best results in both the receiver operating characteristic (ROC) analysis and the decision curve analysis (DCA). This study indicates that CSV-CTCs predominate in CTCs of CRC patients, and a count of CSV-CTCs ≥ 3 is an independent risk factor for worse prognosis.