Li Han, Zhou Chengyuan, Wang Chenjie, Li Bo, Song Yanqiong, Yang Bo, Zhang Yan, Li Xueting, Rao Mingyue, Zhang Jianwen, Su Ke, He Kun, Han Yunwei
Department of Oncology, The Affiliated Hospital of Southwest Medical University, Taiping Street, Luzhou, 646000, Sichuan Province, China.
Department of General Surgery (Hepatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Clin Transl Oncol. 2025 Jan;27(1):309-318. doi: 10.1007/s12094-024-03588-0. Epub 2024 Jul 4.
In AFP-negative hepatocellular carcinoma patients, markers for predicting tumor progression or prognosis are limited. Therefore, our objective is to establish an optimal predicet model for this subset of patients, utilizing interpretable methods to enhance the accuracy of HCC prognosis prediction.
We recruited a total of 508 AFP-negative HCC patients in this study, modeling with randomly divided training set and validated with validation set. At the same time, 86 patients treated in different time periods were used as internal validation. After comparing the cox model with the random forest model based on Lasso regression, we have chosen the former to build our model. This model has been interpreted with SHAP values and validated using ROC, DCA. Additionally, we have reconfirmed the model's effectiveness by employing an internal validation set of independent periods. Subsequently, we have established a risk stratification system.
The AUC values of the Lasso-Cox model at 1, 2, and 3 years were 0.807, 0.846, and 0.803, and the AUC values of the Lasso-RSF model at 1, 2, and 3 years were 0.783, 0.829, and 0.776. Lasso-Cox model was finally used to predict the prognosis of AFP-negative HCC patients in this study. And BCLC stage, gamma-glutamyl transferase (GGT), diameter of tumor, lung metastases (LM), albumin (ALB), alkaline phosphatase (ALP), and the number of tumors were included in the model. The validation set and the separate internal validation set both indicate that the model is stable and accurate. Using risk factors to establish risk stratification, we observed that the survival time of the low-risk group, the middle-risk group, and the high-risk group decreased gradually, with significant differences among the three groups.
The Lasso-Cox model based on AFP-negative HCC showed good predictive performance for liver cancer. SHAP explained the model for further clinical application.
在甲胎蛋白(AFP)阴性的肝细胞癌患者中,预测肿瘤进展或预后的标志物有限。因此,我们的目标是为这一亚组患者建立一个最佳预测模型,采用可解释的方法来提高肝癌预后预测的准确性。
本研究共招募了508例AFP阴性的肝癌患者,用随机划分的训练集进行建模,并用验证集进行验证。同时,将不同时间段治疗的86例患者作为内部验证。在比较基于Lasso回归的Cox模型和随机森林模型后,我们选择了前者来构建我们的模型。该模型已用SHAP值进行了解释,并使用ROC、DCA进行了验证。此外,我们通过采用独立时间段的内部验证集再次确认了模型的有效性。随后,我们建立了一个风险分层系统。
Lasso-Cox模型在1年、2年和3年时的AUC值分别为0.807、0.846和0.803,Lasso-RSF模型在1年、2年和3年时的AUC值分别为0.783、0.829和0.776。本研究最终采用Lasso-Cox模型预测AFP阴性肝癌患者的预后。模型纳入了BCLC分期、γ-谷氨酰转移酶(GGT)、肿瘤直径、肺转移(LM)、白蛋白(ALB)、碱性磷酸酶(ALP)和肿瘤数量。验证集和单独的内部验证集均表明该模型稳定且准确。利用风险因素建立风险分层,我们观察到低风险组、中风险组和高风险组的生存时间逐渐降低,三组之间存在显著差异。
基于AFP阴性肝癌的Lasso-Cox模型对肝癌显示出良好的预测性能。SHAP对模型进行了解释,便于进一步临床应用。