Zhu Jun, Hao Jun, Ma Qian, Shi Tingyu, Wang Shuai, Yan Jingchuan, Chen Rujie, Xu Dong, Jiang Yu, Zhang Jian, Li Jipeng
State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Department of Experiment Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Front Oncol. 2021 Apr 16;11:661040. doi: 10.3389/fonc.2021.661040. eCollection 2021.
Emerging evidence shows that serum tumor biomarkers (TBs) and log odds of positive lymph node scheme (LODDS) are closely associated with the prognosis of colorectal cancer (CRC) patients. The aim of our study is to validate the predictive value of TBs and LODDS clinically and to develop a robust prognostic model to predict the overall survival (OS) of patients with CRC.
CRC patients who underwent radical resection and with no preoperative chemotherapy were enrolled in the study. The eligible population were randomized into training (70%) and test (30%) cohorts for the comprehensive evaluation of the prognostic model. Clinical implications of serum biomarkers and LODDS were identified by univariate and multivariate Cox proportion regression analysis. The predictive ability and discriminative performance were evaluated by Kaplan-Meier (K-M) curves and receiver operating characteristic (ROC) curves. Clinical applicability of the prognostic model was assessed by decision curve analysis (DCA), and the corresponding nomogram was constructed based on the above factors.
A total of 1,202 eligible CRC patients were incorporated into our study. Multivariable COX analysis demonstrated that CA199 (HR = 1.304), CA125 (HR = 1.429), CEA (HR = 1.307), and LODDS (HR = 1.488) were independent risk factors for OS (all P < 0.0001). K-M curves showed that the high-risk group possessed a shorter OS than the low-risk counterparts. The area under curves (AUCs) of the model for 1-, 3- and 5-year OS were 86.04, 78.70, and 76.66% respectively for the train cohort (80.35, 77.59, and 74.26% for test cohort). Logistic DCA and survival DCA confirmed that the prognostic model displayed more clinical benefits than the conventional AJCC 8 TNM stage and CEA model. The nomograms were built accordingly, and the calibration plot for the probability of survival at 3- or 5-years after surgery showed an optimal agreement between prediction and actual observation.
Preoperative serum TBs and LODDS have significant clinical implications for CRC patients. A novel prognostic model incorporating common TBs (CA199, CA125, and CEA) and LODDS displayed better predictive performance than both single factor and the TNM classification. A novel nomogram incorporating TBs and LODDS could individually predict OS in patients with CRC.
新出现的证据表明，血清肿瘤生物标志物（TBs）和阳性淋巴结转移概率对数（LODDS）与结直肠癌（CRC）患者的预后密切相关。我们研究的目的是在临床上验证TBs和LODDS的预测价值，并开发一个强大的预后模型来预测CRC患者的总生存期（OS）。
纳入接受根治性切除且术前未进行化疗的CRC患者。将符合条件的人群随机分为训练组（70%）和测试组（30%），用于对预后模型进行综合评估。通过单因素和多因素Cox比例回归分析确定血清生物标志物和LODDS的临床意义。通过Kaplan-Meier（K-M）曲线和受试者工作特征（ROC）曲线评估预测能力和判别性能。通过决策曲线分析（DCA）评估预后模型的临床适用性，并基于上述因素构建相应的列线图。
共有1202例符合条件的CRC患者纳入我们的研究。多变量COX分析表明，CA199（HR = 1.304）、CA125（HR = 1.429）、CEA（HR = 1.307）和LODDS（HR = 1.488）是OS的独立危险因素（所有P < 0.0001）。K-M曲线显示，高危组的OS比低危组短。训练组模型预测1年、3年和5年OS的曲线下面积（AUC）分别为86.04%、78.70%和76.66%（测试组分别为80.35%、77.59%和74.26%）。逻辑DCA和生存DCA证实，该预后模型比传统的美国癌症联合委员会（AJCC）第8版TNM分期和CEA模型显示出更多的临床益处。据此构建了列线图，术后3年或5年生存概率的校准图显示预测与实际观察之间具有最佳一致性。
术前血清TBs和LODDS对CRC患者具有重要的临床意义。一种包含常见TBs（CA199、CA125和CEA）和LODDS的新型预后模型比单因素和TNM分类显示出更好的预测性能。一种包含TBs和LODDS的新型列线图可以单独预测CRC患者的OS。
