Evaluation of the Role of Circulating Tumor Cells and Microsatellite Instability Status in Predicting Outcome of Advanced CRC Patients

Abstract

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death due to its high metastatic potential. This study aimed to investigate the detection and heterogeneity of circulating tumor cells (CTCs) and the microsatellite instability (MSI) status in advanced CRC patients prior to any systemic front-line treatment. Peripheral whole blood was obtained from 198 patients. CTCs were detected using double immunofluorescence and a real time-polymerase chain reaction assay; whereas MSI status was evaluated using fragment analysis. Median age of the patients was 66 years, 63.1% were males, 65.2% had a colon/sigmoid tumor location and 90.4% had a good performance status (PS). MSI-High status was detected in 4.9% of the patients; 33.3%, 56.1% and 8.6% patients had at least one detectable CEACAM5+/EpCAM+, CEACAM5+/EpCAM− and CEACAM5−/EpCAM+ CTC, respectively, and 9.1% of the patients had CEACAM5mRNA-positive CTCs. Following multivariate analysis, age, PS and MSI were confirmed as independent prognostic factors for decreased time to progression, whereas age, PS and CTC presence were confirmed as independent prognostic factors for decreased overall survival. In conclusion, our data support the use of CEACAM5 as a dynamic adverse prognostic CTC biomarker in patients with metastatic CRC and MSI-High is considered an unfavorable prognostic factor in metastatic CRC patient tumors.

Application of Circulating Tumor Cells and Circulating Free DNA from Peripheral Blood in the Prognosis of Advanced Gastric Cancer

“…Zhang et al tested CTC in patients with bladder cancer planned for surgery and found that 44 cases (86.3%) were positive [35]. Many studies revealed that the detection of CTC in patients with colorectal cancer (CRC) [36], nonsmall cell lung cancer (NSCLC) [37], prostate cancer [38], and so on could predict the outcomes of the patients.…”

Utilization of Circulating Tumor Cells in the Management of Solid Tumors

“…In a study of 121 patients with advanced colorectal cancer, of whom 71 were CTC-positive, CTC positivity was predictive of the depth of invasion, lymphatic involvement, distant metastatic disease, TNM staging, and serum CEA level, and was overall predictive of less favorable PFS and OS, with persistent presence during chemotherapy also associated with poorer PFS and OS [104]. Additional studies have correlated baseline CTC count ≥3/7.5 mL with stage IV disease at diagnosis, at least three sites of metastasis, elevated CEA levels, and increased TNM staging [105,106]. Beyond disease characteristics, additional studies have supported the negative prognostication associated with CTC detection in both localized and advanced CRC prior to intervention [107][108][109][110].…”