基于列线图探索脑内皮黏附分子表达水平在结肠癌预后预测中的作用

Analysis of the prognostic value of cerebral endothelial cell adhesion molecule expression level in colon cancer based on nomogram

目的:探索脑内皮细胞黏附分子(CERCAM)与结肠癌患者预后的关系,利用Cox模型建立具有良好预后判断价值的列线图并予以验证。方法:下载TCGA及GTEx数据库中结肠癌及正常组织中CERCAM表达及患者临床特征数据,收集2013年2月至2019年6月南京市第一医院收治的4例结肠癌患者的癌及癌旁组织样本进行验证,通过差异分析、通路富集分析以及生存分析等方法探索CERCAM的组织定位、功能及预后价值。通过Cox回归筛选出结肠癌的预后危险因素,基于CERCAM及各危险因素构建列线图,分别使用一致性指数、校准曲线、时间依赖性受试者工作特征(ROC)曲线进行验证与评价,根据危险分层绘制生存曲线。结果:结肠肿瘤组织中CERCAM基因的表达水平显著低于正常组织(P<0.001),在结肠癌患者中,CERCAM高表达人群OS(P=0.034)及存活状态(P=0.002)显著劣于低表达组,且CERCAM与癌症信号通路以及PI3K-Akt信号通路的活化有关联。Cox分析显示,CERCAM表达水平(HR=2.23,P=0.015)、T分期(HR=5.64,P=0.015)、M分期(HR=2.62,P=0.022)是结肠癌预后的独立危险因素,血管浸润(HR=2.30,P=0.089)是危险因素,利用上述因素建立列线图,一致性指数提示其区分度好,且训练集与测试集一致;校准曲线、ROC曲线同样显示该列线图的预测能力较好。通过危险分层绘制生存曲线,结果提示高风险组有更低的生存率(P<0.000 1)。结论:CERCAM高表达与结肠癌患者不良预后密切相关,且可能与癌症中蛋白聚糖及PI3K-Akt信号通路有关联,基于CERCAM建立的列线图优于传统预测模型,对结肠癌患者生存预后的评估具有一定临床价值,这种实用的模型有助于患者风险分层及治疗方案的优化。

Objective: To explore the relationship between cerebral endothelial cell adhesion molecule(CERCAM) and prognosis of colon cancer patients, so as to establish a nomogram with good prognostic value by using Cox model and verify its diagnostic value.Methods: The expression profile of CERCAM in colon cancer tissues and normal tissues as well as clinicopathologic data of colon cancer patients were downloaded from TCGA and GTEx databases. At the same time, colon cancer and paracancerous tissue samples collected from 4 colon cancer patients admitted to Nanjing First Hospital from Feburary 2013 to June 2019 were used for verification.Firstly, differential analysis, pathway enrichment analysis, and survival analysis were performed to investigate the tissue localization,functional and prognostic value of CERCAM expression. In addition, Cox regression analyses was conducted to screen the risk factors for the prognosis of colon cancer. A nomogram was established based on CERCAM and various risk factors, and was verified and evaluated by concordance indices, calibration curves, and time-dependent receiver operating characteristic(ROC) curves. In addition,the survival curves were plotted according to risk stratification. Results: The expression of CERCAM in colon cancer tissues was significantly lower than that in normal tissues(P<0.001). The overall survival(P=0.032) and survival status(P=0.002) of colon cancer patients with high CERCAM expression level was significantly inferior to those with low CERCAM expression level. CERCAM was correlated with the activation of proteoglycans in cancer and PI3K-Akt signaling pathway. Cox analysis showed that CERCAM expression level(HR=2.22, P=0.015), T stage(HR=5.65, P=0.015), M stage(HR=2.62, P=0.022) were independent risk factors for prognosis of colon cancer, while vascular infiltration(HR=2.30, P=0.089) was a risk factor as well. Based on the above factors, a nomogram was established. The concordance indices suggested good discrimination of the nomogram, and the training set was consistent with the test set. The calibration curves and ROC curves also indicated good predictive ability of the nomogram. Survival curves plotted according to risk stratification suggested that the high-risk group had lower survival rates(P<0.000 1). Conclusion: High level CERCAM expression is correlated with the poor prognosis of colon cancer patients, which is possibly associated with proteoglycans in cancer and PI3K-Akt signal pathway. The nomogram established based on CERCAM is superior to the traditional prediction model,which has certain clinical value in predicting survival prognosis of colon cancer patients. This practical model is helpful for the risk stratification and the optimization of treatment plan.