Effects of T helper type 1 cells to T helper type 2 cells ratio and the related cytokines on the prognosis of patients with colorectal cancer / 肿瘤研究与临床

ABSTRACT

Objective:To explore effects of T helper type 1 cells (Th1) to T helper type 2 cells (Th2) ratio and the related cytokines on the prognosis of patients with colorectal neoplasms.Methods:A total of 98 colorectal neoplasms patients undergoing the surgery admitted in Suqian Hospital Affiliated to Xuzhou Medical University from December 2015 to December 2017 were enrolled, and all patients were selected as the colorectal cancer group. According to Dukes staging criteria, patients were divided into stage A (25 cases), stage B (30 cases) and stage C (43 cases). In addition, 72 healthy subjects who underwent physical examination in Suqian Hospital Affiliated to Xuzhou Medical University during the same period were selected as the healthy control group. Preoperative venous blood on an empty stomach was extracted from the healthy control group and the colorectal cancer group. Flow cytometry was used to analyze the Th1/Th2 ratio in peripheral blood. The levels of cytokines interferon (IFN)-γ, interleukin (IL)-2, IL-4 and IL-10 in serum samples were detected by using enzyme-linked immunosorbent assay (ELISA). After operation, patients were followed up by telephone or outpatient service. The Th1/Th2 ratio and levels of IFN-γ, IL-2, IL-4 and IL-10 of both groups at different stages of both groups were compared. The correlation between Th1/Th2 ratio and the clinicopathological characteristics of colorectal cancer patients was analyzed. Kaplan-Meier method was used to make survival analysis and Cox regression model was used to analyze influencing factors for overall survival (OS).Results:The Thl/Th2 ratio in colorectal cancer patients was lower than that in the healthy control group (5.13±2.04 vs. 11.82±2.76, t = 18.177, P < 0.01). The lymphovascular invasion and Dukes stage C ratio in patients with decreased Th1/Th2 ratio were higher than those in patients with increased Th1/Th2 ratio ( χ2 values were 16.403, 16.248, both P < 0.01). The levels of IFN-γ and IL-2 in serums of colorectal patients were (95±15) ng/L and (78±10) ng/L, respectively, which were lower than those in the healthy control group [(157±17) ng/L and (123±12) ng/L, t values were 25.160, 26.622, all P < 0.01]. The levels of IL-4 and IL-10 in the colorectal cancer group were (87±16) ng/L and (178±18) ng/L, respectively, which were higher than those in the healthy control group [(46±9) ng/L and (124±12) ng/L] ( t values were 19.577, 22.095, all P < 0.01). The follow-up time ranged from 31.0 to 55.0 months, and the median follow-up time was 37.2 months and the median OS time was 21.0 months. Survival analysis showed that the OS of patients with increased Th1/Th2 ratio was better than that of patients with reduced Th1/Th2 ratio ( χ2 = 7.287, P = 0.007). Multivariate Cox regression analysis showed that lymph node metastasis, tumor stage, and Th1/Th2 ratio were independent influencing factors for OS in colorectal cancer patients ( OR values were 8.541, 3.442, 1.275, all P < 0.05). Conclusion:The imbalance of related cytokines secreted by Th1 and Th2 cells and the decrease in the ratio of Th1/Th2 are related to the progression and the poor prognosis of colorectal cancer.