基于组织芯片技术的结直肠癌患者化疗反应性预测模型构建分析

Construction and analysis of a predictive model for chemotherapy response of patients with colorectal cancer based on tissue chip technology

目的探讨组织芯片技术的结直肠癌患者化疗反应性预测模型。方法前瞻性选取2017年1月至2019年12月宁波大学附属人民医院均已接受规范化疗治疗的217例结直肠癌患者,按照7∶3比例随机分为训练集(152例)和测试集(65例),随访6个月,根据RECIST 1.1实体瘤疗效评价标准评价化疗反应性分为反应性良好和反应性不良组。比较训练集患者的临床资料,并应用组织芯片技术分析患者Ang-2、caspase-3和CD147的表达水平,应用Logistic回归模型分析影响结直肠癌化疗反应性的相关因素,采用R软件基于训练集建立列线图预测模型,并在测试集评估模型效能。结果训练集中排除失访1例,最终纳入151例,其中化疗反应良好组93例,化疗反应不良组58例,化疗反应不良组肿瘤直径、血清癌胚抗原、caspase3、Ang2表达水平、临床分期IV期比例显著高于化疗反应良好组(均P<0.05);Logistic回归显示肿瘤直径(OR=2.394)、血清癌胚抗原(OR=1.878)、caspase-3(OR=4.261)、Ang-2表达水平(OR=5.457)、临床分期IV期(OR=5.954)为结直肠癌患者药物反应不良的独立危险因素(均P<0.05),预测结直肠癌患者化疗反应不良相关因素的一致性指数(C-index)为0.915。外部验证显示敏感性为86.96%,特异性为92.50%,准确率为90.48%(42/65)。结论Ang2、caspase3表达水平与结直肠癌化疗反应性相关,可作为评价结直肠癌化疗反应性的预测指标。

Objective To explore the prediction model of tissue chip technology for the chemotherapy response of patients with colorectal cancer.Methods 217 patients with colorectal cancer who had received standardized chemotherapy in the Affiliated People’s Hospital of Ningbo University from Jan.2017 to Dec.2019 were prospectively selected.The patients were randomly divided into training set(152 cases)and test set(65 cases)according to the ratio of 7:3,and were followed up for 6 months.The clinical data of the patients in the training set were compared,the expression levels of Ang-2,caspase-3 and CD147 in the patients were analyzed by tissue microarray technology,and the related factors affecting the responsiveness of colorectal cancer chemotherapy were analyzed by the Logistic regression model.R software was used based on the training set.A nomogram prediction model was built and model performance on the test set was evaluated.Results One case was excluded from the training center,and 151 cases were finally included,including 93 cases in the chemotherapy response group and 58 cases in the chemotherapy response group.The tumor diameter,serum carcinoembryonic antigen,caspase3,Ang2 expression level,and the proportion of clinical stage IV in the poor chemotherapy group were significantly higher than those in the good chemotherapy group(all P<0.05);Logistic regression showed tumor diameter(OR=2.394),serum carcinoembryonic antigen(OR=1.878),caspase-3(OR=4.261),Ang-2 expression level(OR=5.457),and clinical stage IV(OR=5.954)were independent risk factors for adverse drug reactions in patients with colorectal cancer(all P<0.05).The consistency index(C-index)for predicting the factors related to adverse chemotherapy reactions in patients with colorectal cancer was 0.915.External verification showed that the sensitivity was 86.96%,the specificity was 92.50%,and the accuracy was 90.48%(42/65).Conclusion The expression levels of Ang-2 and caspase-3 are correlated with the responsiveness of colorectal cancer to chemotherapy,and can be used as predictive indicators to evaluate the responsiveness of colorectal cancer to chemotherapy.