CTC、MDSCs及S100A9水平对Ⅱ~Ⅲ期结直肠癌术后临床预后的评估价值

Evaluation value of CTC, MDSCs and S100A9 levels in postoperative clinical prognosis of stage Ⅱ-Ⅲ colorectal cancer

目的:探讨外周血循环肿瘤细胞(CTC)及外周血髓源抑制细胞(MDSCs)、S100钙离子结合蛋白A9(S100A9)水平对Ⅱ~Ⅲ期结直肠癌患者术后临床预后的评估价值。方法:回顾分析山东大学齐鲁医院(青岛)2017年3月—2019年3月收治并行根治术的Ⅱ~Ⅲ期结肠癌患者为观察组(n=210),另选取同期来院进行健康体检者为对照组(n=53),检测两组MDSCs、S100A9水平,对比观察组术前与术后MDSCs、S100A9水平。根据术后肿瘤有无进展将其分为有效组177例,无效组33例,比较两组MDSCs、S100A9水平。采用χ^(2)检验、t检验及受试者工作特征(ROC)曲线进行统计学分析。评价CTC诊断效能。对比不同临床特征结肠癌患者的表达情况,分析影响结肠癌患者术后生存事件的相关因素。结果:观察组术前MDSCs、S100A9水平均明显高于对照组(P<0.05);观察组术后MDSCs、S100A9水平明显低于术前(P<0.05);有效组治疗前MDSCs、S100A9水平均低于无效组(P<0.05);ROC曲线显示,MDSCs、S100A9预测总生存时间的最佳临界值为4.23%和2973.43 pg/mL;210例结肠癌患者中,37例的CTC呈阳性,CTC诊断结肠癌的敏感度为40.22%(37/92),特异度为100%(118/118),阳性预测值为100%(37/37),阴性预测值68.21%(118/1773),准确度为73.81%(155/210);CTC阳性与CTC阴性结肠癌患者的分型、TNM分期、淋巴结转移比较差异有统计学意义(P<0.05);MDSCs与S100A9呈负相关(r=-0.922,P=0.038),CTC、MDSCs、S100A9三者间无相关性(P>0.05);年龄、既往息肉史、肿瘤分型、肿瘤最大径、TNM分期、淋巴结转移、远处转移、MDSCs水平、S100A9水平及CTC个数均对患者生存时间有影响(P<0.05)。结论:MDSCs、S100A9高水平对Ⅱ~Ⅲ期结肠癌患者术后远期预后有良好的预测价值,而CTC可作为预测结肠癌淋巴结转移和预后不良的参考指标。

Objective:To investigate the evaluation value of peripheral blood circulating tumor cells(CTC),peripheral blood myeloid suppressor cells(MDSCs)and S100 calcium-binding protein A9(S100A9)in postoperative prognosis of patients with stageⅡtoⅢcolorectal cancer.Methods:The level of MDSCs and S100A9 in stageⅡ~Ⅲcolon cancer patients admitted to Qilu Hospital of Shandong University(Qingdao)from March 2017 to March 2019 who underwent radical resection were retrospectively analyzed as the observation group(n=210),and healthy subjects who came to qilu Hospital during the same period were selected as the control group(n=53).The levels of MDSCs and S100A9 in the observation group were compared before and after operation.According to the postoperative tumor progression,177 cases were divided into effective group and 33 cases were invalid group.MDSCs and S100A9 levels were compared between the two groups.Chi-square test,T test and receiver operating characteristic curve(ROC)were used for statistical analysis.Evaluate the diagnostic efficiency of CTC.The expression of colon cancer patients with different clinical characteristics was compared,and multivariate analysis was conducted to analyze the related factors affecting postoperative survival events of colon cancer patients.Results:The levels of MDSCs and S100A9 in the observation group were significantly higher than those in the control group(P<0.05).The levels of MDSCs and S100A9 in the observation group were significantly lower than those before surgery(P<0.05).The levels of MDSCs and S100A9 in effective group were lower than those in ineffective group before treatment(P<0.05).ROC curve showed that the optimal critical values of MDSCs and S100A9 for predicting total survival time were 4.23%and 2973.43 pg/mL.Among 210 patients with colon cancer,37 cases were positive for CTC,with sensitivity of 40.22%(37/92),specificity of 100%(118/118),positive predictive value of 100%(37/37),negative predictive value of 68.21%(118/1773)for the diagnosis of colon cancer.The accuracy rate was 73.81%(155/210).The classification,TNM stage and lymph node metastasis of CTC-positive and CTC-negative colon cancer patients were statistically significant(P<0.05).There was a negative correlation between MDSCs and S100A9(r=-0.922,P=0.038),but no correlation between CTC,MDSCs and S100A9(P>0.05).Age,previous polyp history,tumor type,maximum tumor size,TNM stage,lymph node metastasis,distant postoperative metastasis,MDSCs level,S100A9 level and the number of CTC all affected the survival time of patients(P<0.05).Conclusion:High levels of MDSCs and S100A9 have good predictive value for long-term prognosis of stageⅡtoⅢcolorectal cancer patients,while CTC can be used as a reference index for predicting lymph node metastasis and poor prognosis of colorectal cancer patients.