术中腹腔内植入氟尿嘧啶对结直肠癌患者免疫功能及miR-34a、ZEB2表达的影响

Intraperitoneal implantation of 5-fluorouracil on immune function and expression of miR-34a and ZEB2 in colorectal cancer patients

目的探讨术中腹腔内植入氟尿嘧啶(5-Fu)对结直肠癌患者免疫功能及miR-34a、ZEB2表达的改变以及生存影响。方法选择2014年1月至2016年12月在延安大学咸阳医院接受根治性手术治疗的结直肠癌患者92例,采用随机数字表法分为2组,各46例。对照组患者行腹腔镜下结直肠癌根治性切除术,观察组在关腹前给予5-Fu植入剂,术后两组均给予营养支持及预防性使用抗生素。对比两组患者1年生存率、复发率、免疫功能及miR-34a、ZEB2血清表达情况。结果 (1)两组术后住院时间差异无统计学意义(t=0.251、P=0.401)。观察组无病生存时间为(10.26±1.29)个月,显著长于对照组的(8.92±1.02)个月,差异有统计学意义(t=-5.526,P<0.01)。对照组1年生存率为78.26%(95%CI=72.13%～84.39%),观察组1年生存率为95.65%(95%CI=93.91%～97.39%),两组比较,差异有统计学意义(χ2=5.896,P=0.015)。(2)治疗后两组各免疫指标均呈明显下降后升高的趋势(P<0.05),术后2 d时观察组Ig M明显高于对照组(P<0.05),术后7 d时观察组Ig A与CD4+明显低于对照组(P<0.05)。(3)治疗前两组血清mi R-34a及ZEB2蛋白表达水平比较,差异无统计学意义(t=-1.097、1.392,P=0.259、0.138)。治疗后7 d时,观察组和对照组mi R-34a蛋白表达均明显升高(t=3.975、-3.718,P=0.001、0.005),ZEB2蛋白表达明显下降(t=6.279、4.183,均P<0.001),但观察组miR-34a及ZEB2蛋白表达水平的变化幅度较对照组更为明显(t=-2.813、4.118,P=0.029、<0.001)。结论结直肠癌患者术中腹腔内植入5-Fu对患者1年生存率及复发率均无明显影响,但对患者免疫功能有一定抑制作用,可改善miR-34a低表达,抑制ZEB2高表达。

Objective：To investigate the effect of intraperitoneal implantation of 5-fluorouracil（5-Fu） intraperitoneally on immune function and expression of miR-34a and ZEB2 in patients with colorectal cancer. Methods：From January 2014 to December 2016, ninety-two patients with colorectal cancer who underwent radical surgery in Xianyang Hospital of Yan＇an University were selected. They were divided into 2 groups using random number table method, with 46 cases in each group. Patients in the control group underwent elective laparoscopic radical resection of colorectal cancer under general anesthesia. The observation group was given 5-Fu implantation before abdominal closure, and nutritional support and prophylactic antibiotics were given to both groups after operation. The survival rate, relapse rate, immune function, and the expression of miR-34a and ZEB2 between two groups were compared. Results：（1） There was no significant difference in postoperative hospital stay between the two groups （t=0.251, P=0.401）. The disease-free survival time of the observation group was （10.26±1.29） months, which was significantly longer than that of the control group （8.92±1.02） months （t=-5.526, P〈0.01）. The 1-year survival rate of the control group and observation group was 78.26% （95% CI=72.13%-84.39%） and 95.65% （95% CI=93.91%-97.39%）, respectively, with statistically significant difference between the two groups （χ2=5.896, P=0.015）. （2） After treatment, all immune indicators in the two groups showed a significant increase after fall trend （P〈0.05）. The IgM level in the observation group was significantly higher than that in the control group at 2 d after operation （P〈0.05）, and the levels of IgA and CD4＋ in the observation group were significantly lower than those in the control group at 2 d after operation （P〈0.05）. （3） There were no significant differences in serum miR-34a and ZEB2 protein levels between the two groups before treatment （t=-1.097, 1.392; P=0.259, 0.138）. 7 days after treatment, miR-34a in both groups was significantly increased （t=3.975, -3.718; P=0.001, 0.005）, ZEB2 was significantly decreased （t=6.279, 4.183; both P〈0.001）, but the changes of observation group were higher than the control group （t=-2.813, 4.118; P=0.029, 〈0.001）. Conclusions： Intraperitoneal implantation of 5-Fu in colorectal cancer patients has no significant effect on the 1-year survival rate and recurrence rate, but it has a certain inhibitory effect on the immune function of patients. It can improve the low expression of miR-34a and inhibit the high expression of ZEB2.