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《工程(英文)》 >> 2022年 第15卷 第8期 doi: 10.1016/j.eng.2021.06.017

基于人工智能的肺癌NOG/PDX模型驱动基因匹配预测

a School of Medicine, Tongji University, Shanghai 200092, China
b Department of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China
c Department of Automation, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
d Spine Center, Orthopedic Department, Shanghai Changzheng Hospital, Shanghai 200003, China
e Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China
f School of Materials Science and Engineering, Tongji University, Shanghai 201804, China
g Department of Thoracic Surgery, Allegheny General Hospital, Pittsburgh, PA 15212, USA
h Department of Thoracic Surgery and Minimally Invasive Thoracic Surgery Unit (UCTMI), Coruña University Hospital, Coruña 15006, Spain
i Oncology and Immunology BU, Research Service Division, WuXi Apptec, Shanghai 200131, China
j SJTU–Yale Joint Center for Biostatistics and Data Science, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
k Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA

收稿日期: 2020-12-08 修回日期: 2021-05-05 录用日期: 2021-06-20 发布日期: 2021-08-18

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摘要

患者源性肿瘤异种移植物(PDX)是癌症药物发现和筛查的有力工具。然而,目前的研究对PDX的基因型错配知之甚少,导致PDX使用过程中产生巨大的经济损失。在此,本研究建立了53 例肺癌患者的PDX模型,基因型匹配率为79.2%(42/53)。此外,检查了17 个临床病理学特征,并基于最低赤池信息量准则(AIC)、最小绝对收缩和选择算子(LASSO)-逻辑回归(LR)、支持向量机(SVM)递归特征消除(SVM-RFE)、极端梯度增强(XGBoost)、梯度增强和分类特征(CatBoost),以及合成少数过采样技术(SMOTE)输入逐步逻辑回归模型。最后,通过100 个试验组的准确度、受试者工作特征曲线下面积(AUC)和F1 评分评价所有模型的性能。两个多变量 LR 模型显示,年龄、驱动基因突变的数量、表皮生长因子受体(EGFR)基因突变、既往化疗的类型、既往酪氨酸激酶抑制剂(TKI)治疗和样本来源是强有力的预测因素。此外,CatBoost (平均精度= 0.960;平均AUC = 0.939;平均F1 分数= 0.908)和八特征SVM-RFE(平均精度= 0.950;平均AUC = 0.934;平均F1 分数= 0.903)在算法中表现出最好的性能。同时,除CatBoost 外,SMOTE的应用提高了大多数模型的预测能力。基于SMOTE,单一模型的集成分类器达到了最高的准确度(平均值= 0.975)、AUC(平均值= 0.949)和F1 评分(平均值= 0.938)。总之,本文建立了一个最佳预测模型来筛选肺癌患者的NOD/Shi-scid白细胞介素-2受体(IL-2R) γnull(NOG)/PDX模型,并为建立预测模型提供了一种通用方法。

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