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多因素风险预测分析结直肠癌肝转移:程序性细胞死亡配体 1 联合阳性评分及其他因素。

Multifactorial risk prediction analysis of liver metastasis in colorectal cancer: incorporating programmed cell death ligand 1 combined positive score and other factors.

机构信息

Department of General Surgery,The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China.

Department of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China.

出版信息

J Gastrointest Surg. 2024 Aug;28(8):1294-1301. doi: 10.1016/j.gassur.2024.05.032. Epub 2024 May 29.

Abstract

BACKGROUND

The occurrence of liver metastasis significantly affects the prognosis of colorectal cancer (CRC). Existing research indicates that primary tumor location, vascular invasion, lymph node metastasis, and abnormal preoperative tumor markers are risk factors for CRC liver metastasis. Positive expression of programmed cell death ligand 1 (PD-L1) may serve as a favorable prognostic marker for nasopharyngeal and gastric cancers, in which combined positive score (CPS) quantifies the level of PD-L1 expression. This study aimed to explore CPS as a potential risk factor for CRC liver metastasis and integrate other independent risk factors to establish a novel predictive model for CRC liver metastasis.

METHODS

A retrospective analysis was conducted on 437 patients with CRC pathologically diagnosed at The Second Xiangya Hospital of Central South University from January 1, 2019, to December 31, 2021. Data were collected, including CPS, age, gender (male and female), primary tumor location, Ki-67 expression, pathologic differentiation, neural invasion, vascular invasion, lymph node metastasis, and preoperative tumor markers. The optimal cutoff point for the continuous variable CPS was determined using the Youden index, and all CPSs were dichotomized into high- and low-risk groups based on this threshold (scores below the threshold were considered high risk, and score above the threshold were considered low risk). Univariate logistic regression analysis was employed to identify risk factors for CRC liver metastasis, followed by multivariate logistic regression analysis to integrate the selected risk factors. The predictive model was validated through the construction of receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). A nomogram was constructed for visualization.

RESULTS

The determined cutoff point for PD-L1 CPS was 4.5, with scores below this threshold indicating a high risk of CRC liver metastasis. In addition, primary tumor origin other than the rectum, presence of pericolonic lymph node metastasis, and abnormal levels of tumor markers carcinoembryonic antigen and cancer antigen 19-9 were identified as independent risk factors for CRC liver metastasis. The constructed clinical prediction model demonstrated good predictive ability and accuracy, with an area under the ROC curve of 0.871 (95% CI, 0.838-0.904).

CONCLUSION

The exploration and validation of CPS as a novel predictor of CRC liver metastasis were performed. Based on these findings, a new clinical prediction model for CRC liver metastasis was developed by integrating other independent risk factors. The DCA, clinical impact curve, and nomogram graph constructed on the basis of this model have significant clinical implications and guide clinical practice.

摘要

背景

肝转移的发生显著影响结直肠癌(CRC)的预后。现有研究表明,原发肿瘤位置、血管侵犯、淋巴结转移和术前肿瘤标志物异常是 CRC 肝转移的危险因素。程序性死亡配体 1(PD-L1)的阳性表达可能是鼻咽癌和胃癌的有利预后标志物,其中联合阳性评分(CPS)量化 PD-L1 表达水平。本研究旨在探讨 CPS 作为 CRC 肝转移的潜在危险因素,并整合其他独立危险因素,建立 CRC 肝转移的新型预测模型。

方法

对 2019 年 1 月 1 日至 2021 年 12 月 31 日在中南大学湘雅二医院经病理诊断为 CRC 的 437 例患者进行回顾性分析。收集的数据包括 CPS、年龄、性别(男、女)、原发肿瘤位置、Ki-67 表达、病理分化、神经侵犯、血管侵犯、淋巴结转移和术前肿瘤标志物。使用约登指数确定连续变量 CPS 的最佳截断点,根据该阈值将所有 CPS 分为高风险和低风险组(低于阈值的分数被认为是高风险,高于阈值的分数被认为是低风险)。采用单因素逻辑回归分析确定 CRC 肝转移的危险因素,然后采用多因素逻辑回归分析整合选定的危险因素。通过构建受试者工作特征(ROC)曲线、校准曲线和决策曲线分析(DCA)来验证预测模型。并构建可视化的列线图。

结果

PD-L1 CPS 的截断点为 4.5,低于该阈值的分数提示 CRC 肝转移的风险较高。此外,原发肿瘤起源于直肠以外、存在结肠旁淋巴结转移以及肿瘤标志物癌胚抗原和癌症抗原 19-9 异常被确定为 CRC 肝转移的独立危险因素。所构建的临床预测模型具有良好的预测能力和准确性,ROC 曲线下面积为 0.871(95%CI,0.838-0.904)。

结论

本研究探索并验证了 CPS 作为 CRC 肝转移的新型预测因子。在此基础上,通过整合其他独立危险因素,建立了 CRC 肝转移的新临床预测模型。在此模型基础上构建的 DCA、临床影响曲线和列线图具有重要的临床意义,指导临床实践。

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