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基于实验室参数的机器学习模型用于术前预测胶质瘤中Ki-67表达的开发与验证

Development and validation of a machine learning model based on laboratory parameters for preoperative prediction of Ki-67 expression in gliomas.

作者信息

Huang Jinlan, Ding Shoupeng, Lin Lijin, Zhong Guiyang, Yu Zhou, Luo Qingwen, Chen Dongmei, Chen Yazhi, Zheng Shouzhao, Zheng Shihao

机构信息

1Department of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Gene Diagnosis Research Center, Fujian Clinical Research Center for Laboratory Medicine of Immunology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian.

2Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian.

出版信息

J Neurosurg. 2025 Mar 28:1-13. doi: 10.3171/2024.11.JNS241673.

Abstract

OBJECTIVE

Glioma is the most common form of brain tumor and has high mortality. The Ki-67 proliferation index, a vital marker of cell proliferation, has been demonstrated to predict tumor classification and prognosis. The aim of this study was to develop and validate a noninvasive model based on machine learning (ML) and routine laboratory parameters to preoperatively predict the level of Ki-67 in gliomas.

METHODS

A total of 506 patients with pathological confirmation of glioma from 2 medical centers (January 2020 to December 2023) were retrospectively enrolled and divided into training (n = 352), internal validation (n = 88), and external validation (n = 66) cohorts. According to the Ki-67 proliferation index, patients were classified into low Ki-67 (index < 10%) and high Ki-67 (index ≥ 10%) groups. Laboratory parameters were obtained within 1 week before surgery from the Laboratory Information System. The potential features associated with Ki-67 levels were screened using extreme gradient boosting (XGBoost), support vector machine (SVM), and least absolute shrinkage and selection operator (LASSO). Then, 10 ML classifiers, including SVM, XGBoost, logistic regression (LR), random forest, adaptive boosting (AdaBoost), gradient boosting machine, partitioning around medoids, naive Bayes, neural network, and bagged classification and regression trees (CART), were trained. The performance of these models was evaluated on internal and external validation sets using the area under the receiver operating characteristic curve (AUC). Calibration curve, decision curve, and clinical impact curve analyses were used for validation.

RESULTS

Fifteen laboratory parameters that met the requirements of XGBoost, SVM, and LASSO were selected. Among all tested ML models, the LR model had superior performance with relatively high AUC, accuracy, sensitivity, and specificity. The LR model achieved AUCs of 0.838 in the training set, 0.800 (with the highest accuracy [0.782] and optimal sensitivity [0.845]) in the internal validation set, and 0.757 in the external validation set. Finally, the LR model was visualized as a nomogram based on the top 6 laboratory parameters (age, anion gap, apolipoprotein A-1, apolipoprotein B, calcium, creatinine) to individually predict the Ki-67 proliferation index in patients with gliomas.

CONCLUSIONS

The authors successfully constructed an LR model based on routine laboratory parameters, with relatively high sensitivity and specificity, to preoperatively predict the level of Ki-67 in patients with gliomas, which might be helpful for prognostic evaluation and clinical decision-making.

摘要

目的

胶质瘤是最常见的脑肿瘤形式,死亡率高。Ki-67增殖指数是细胞增殖的重要标志物,已被证明可预测肿瘤分类和预后。本研究的目的是开发并验证一种基于机器学习(ML)和常规实验室参数的非侵入性模型,以术前预测胶质瘤中Ki-67的水平。

方法

回顾性纳入2个医学中心(2020年1月至2023年12月)共506例经病理证实的胶质瘤患者,并分为训练组(n = 352)、内部验证组(n = 88)和外部验证组(n = 66)。根据Ki-67增殖指数,将患者分为低Ki-67(指数<10%)和高Ki-67(指数≥10%)组。术前1周内从实验室信息系统获取实验室参数。使用极端梯度提升(XGBoost)、支持向量机(SVM)和最小绝对收缩和选择算子(LASSO)筛选与Ki-67水平相关的潜在特征。然后,训练包括SVM、XGBoost、逻辑回归(LR)、随机森林、自适应提升(AdaBoost)、梯度提升机、围绕中心点划分、朴素贝叶斯、神经网络以及袋装分类和回归树(CART)在内的10种ML分类器。使用受试者操作特征曲线(AUC)下面积在内部和外部验证集上评估这些模型的性能。采用校准曲线、决策曲线和临床影响曲线分析进行验证。

结果

选择了15个符合XGBoost、SVM和LASSO要求的实验室参数。在所有测试的ML模型中,LR模型具有卓越的性能,具有相对较高的AUC、准确性、敏感性和特异性。LR模型在训练集中的AUC为0.838,在内部验证集中的AUC为0.800(准确性最高[0.782],敏感性最佳[0.845]),在外部验证集中的AUC为0.757。最后,基于前6个实验室参数(年龄、阴离子间隙、载脂蛋白A-1、载脂蛋白B、钙、肌酐)将LR模型可视化成列线图,以单独预测胶质瘤患者的Ki-67增殖指数。

结论

作者成功构建了一种基于常规实验室参数的LR模型,具有相对较高的敏感性和特异性,可术前预测胶质瘤患者的Ki-67水平,这可能有助于预后评估和临床决策。

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