Monitoring and Prognostic Analysis of Peripheral Blood Circulating Tumor Cell Before and After Operation for Early and Middle Stage Colorectal Cancer / 中山大学学报(医学科学版)

ABSTRACT

@#【Objective】To study the relationship between circulation tumor cell（CTC）and clinicopathological characteristics in early and middlestage colorectal cancer，and to evaluate the diagnostic and prognostic value of peripheral blood CTC through dynamically monitoring the changes of peripheral blood CTC in the patients before and after operation.【Methods】 Prospectively 67 patients with early and middle stage colorectal cancer were included，and 20 healthy volunteers served as contrast during the same period. Peripheral venous blood（7.5 mL）was collected 24 h before radical operation，3 months after radical operation and in control group. SE- iFISH technique was used to isolate and identify CTC. The cutoff value of CTC in diagnosis of colorectal cancer was determined by the receiver operating curve（ROC）and Youden index. Kaplan-Meier and log-rank methods were used for survival analysis and multivariate COX regression analysis for multivariate correction. The value of CTC in the diagnosis of early and middle stage colorectal cancer was evaluated comprehensively，and then the relationship between CTC in peripheral blood and clinicopathological characteristics and prognosis was synthetically evaluated combined with clinicopathological characteristics and postoperative follow- up data. 【Results】The positive rate of CTC in patients with early and middle stage colorectal cancer was significantly higher than that in healthy people（91.0% vs. 5.0% ，P<0.01）. The CTC enumeration was significantly correlated with the depth of invasion and tumor location（P = 0.001，P = 0.044），but not with gender，age，tumor size，lymph node metastasis，TNM stage ，CEA level and CA-199 level. The preoperative CTC enumeration were not correlated with the above-mentioned clinicopathological parameters. Preoperative CTC had no predictive significance for disease free survival（DFS）and total survival（OS）（AUC = 0.359，P = 0.068；AUC = 0.428，P = 0.423），and postoperative CTC critical point of 3/7.5 mL had predictive significance for DFS and OS（AUC = 0.936 ，P < 0.001 ；AUC = 0.863 ，P < 0.001）. It was found that patients with early and middle stage colorectal cancer were divided into two groups ：good prognosis group（CTC < 3 after operation or the number of CTC after operation was equal or decreased with the number of CTC before operation）and bad prognosis group（CTC ≥ 3 after operation or the number of CTC after operation was higher than the number of CTC before operation）. The DFS of the good prognosis group was significantly longer than that of the poor prognosis group （43.7 months vs. 20.4 months，P < 0.001；48.7 months vs. 26.8 months，P < 0.001），and the OS was also significantly longer （54.7 months vs. 43.3 months，P < 0.001；54.8 months vs. 45.1 months，P < 0.001）. Multivariate analysis showed that CTC ≥ 3/7.5 mL was a bad independent factor of DFS and OS.【Conclusions】CTC has high clinical value in patients with early and middle stage colorectal cancer. Preoperative CTC values can not predict the prognosis of early and middle stage colorectal cancer ，but postoperative CTC values and dynamic detection for CTC changes before and after operation can independently predict the prognosis of early and middle stage colorectal cancer.