Predictive Value of Circulating Tumor Cells in Prognosis of Stage III/IV Colorectal Cancer After Oxaliplatin-based First-line Chemotherapy

Abstract

Background/aim: Insufficient data exist to support the concept of the circulating tumor cell (CTC) level as a prognostic factor for platinum-based first-line chemotherapy. This study investigated the impact of CTCs on the prognosis of patients with advanced colorectal cancer (CRC) after receiving platinum-based chemotherapy. Analyses were carried out of clinicopathological features and molecular phenotypes to clarify independent risk factors for a high CTC count.

Patients and methods: Patients diagnosed with stage III/IV CRC (n=76) were included in the study. The blood samples of patients were evaluated for CTCs using the CellRich™ platform system. Immunohistochemistry (Ias used to analyze epithelial-mesenchymal transition-associated biomarkers E-cadherin and vimentin. Univariate and logistic regression analyses were then conducted to analyze the risk factors for CTC expression. Additionally, the influence of oxaliplatin on disease-free survival after first-line chemotherapy or during chemotherapy was analyzed through a 2-year follow-up.

Results: Patients in the CTC⁺ group experienced shorter DFS after receiving oxaliplatin first-line chemotherapy than patients in the CTC^- group (p<0.01). In addition, univariate analysis revealed that the tumor M-stage, tumor location, RAS mutation, high expression of vimentin, and deletion of E-cadherin expression were correlated with a high CTC count. Multivariate analysis suggested that the presence of RAS gene mutations and high vimentin expression were independent risk factors for high CTC loads (p<0.01).

Conclusion: CTC positivity can indicate the efficacy of first-line chemotherapy with oxaliplatin in stage III/IV colorectal cancer. This may be linked to tumor epithelial-mesenchymal transition in patients with CTCs. Moreover, RAS gene mutation and high expression of vimentin were identified as independent risk factors for a high CTC count.

Keywords: Circulating tumor cells; adjuvant chemotherapy; colorectal cancer; disease-free survival.