肿瘤标志物和Ki67在结直肠癌中的表达及预后因素分析

Prognostic analysis of combining preoperative serum tumor markers and Ki67 label index in patients with colorectal cancer

目的探讨术前血清肿瘤标志物与术后Ki67联合检测对结直肠癌病人预后评估的价值。方法收集2012年1月至2014年6月在武汉大学人民医院胃肠外科就诊的结直肠癌病人的临床病理资料和随访资料。癌胚抗原(CEA)>5μg/L定义为阳性,癌抗原(CA)19-9>35 kU/L定义为阳性。Ki67 LI大于其对应截断值定义为高表达(阳性)。绘制受试者工作特征(ROC)曲线寻找Ki67 LI的截断值[曲线下面积(AUC)最大时];Cox回归分析寻找影响结直肠癌病人预后的独立危险因素。结果研究共纳入311例结直肠癌病人,截至2019年6月1日,中位随访67个月(3~89个月),随访率94.2%,病死率32.5%。单因素生存分析提示,CEA阳性、CA19-9阳性,Ki67高表达与结直肠癌病人预后不良相关(均P<0.01)。联合血清肿瘤标志物和Ki67的生存分析结果提示,均阴性时病人预后最好,单阳性时次之,均阳性时最差(均P<0.01)。Cox回归结果提示:CEA[HR=6.461,95%CI(3.693,11.304),P<0.01]、CA19-9[HR=2.046,95%CI(1.214,3.449),P=0.007]、TNM[HR=2.104,95%CI(1.597,5.242),P=0.028]、CEA+Ki67[HR=9.992,95%CI(5.337,18.706),P<0.01]、CA19-9+Ki67[HR=5.345,95%CI(2.282,12.521),P<0.01]是影响预后的独立危险因素。结论联合检测术前血清肿瘤标志物和术后Ki67指标对评估结直肠癌病人预后具有重要价值。

Objective To explore the prognostic value of preoperative serum tumor markers plus postoperative Ki67 detection in patients with colorectal cancer.Methods From January 2012 to June 2014,clinicopathological data of colorectal cancer patients receiving surgery treatment were collected.CEA>5μg/L was defined as positive;CA19-9>35 kU/L was defined as positive;Ki67 LI greater than its cut-off value was defined as high expression(positive).Receiver operating characteristic(ROC)curve was utilized for determining the cut-off value(with the greatest area under the curve)of Ki67 LI.Cox regression was employed for performing risk factor analysis.Results A total of 311 patients with colorectal cancer were recruited.As of June 1,2019,they were followed up for 67(3-89)months with a follow-up rate of 94.2%and a mortality rate of 32.5%.Univariate survival analysis revealed that CEA positivity,CA19-9 positivity and high Ki67 expression were associated with poor prognosis in colorectal cancer patients(all P<0.01).The results of survival analysis plus serum tumor markers and Ki67 showed that the prognosis was the best when all parameters were negative,followed by those when single positive and the worst when all parameters positive(all P<0.01).Cox regression results indicated that CEA[HR=6.461,95%CI(3.693,11.304),P<0.01],CA19-9[HR=2.046,95%CI(1.214,3.449),P=0.007],TNM[HR=2.104,95%CI(1.597,5.242),P=0.028],CEA+Ki67[HR=9.992,95%CI(5.337,18.706),P<0.01]and CA19-9+Ki67[HR=5.345,95%CI(2.282,12.521),P<0.01]were independent risk factors affecting prognosis.Conclusion The combined detection of preoperative serum tumor markers and postoperative Ki67 markers is of great value in evaluating the prognosis of patients with colorectal cancer.