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基于 21 基因分子预后评分系统的透明细胞肾细胞癌总生存人工智能预测模型。

Artificial intelligence prediction model for overall survival of clear cell renal cell carcinoma based on a 21-gene molecular prognostic score system.

机构信息

Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Institute of Radiotherapy and Oncology, Soochow University, Suzhou, China.

出版信息

Aging (Albany NY). 2021 Mar 3;13(5):7361-7381. doi: 10.18632/aging.202594.

Abstract

We developed and validated a new prognostic model for predicting the overall survival in clear cell renal cell carcinoma (ccRCC) patients. In this study, artificial intelligence (AI) algorithms including random forest and neural network were trained to build a molecular prognostic score (mPS) system. Afterwards, we investigated the potential mechanisms underlying mPS by assessing gene set enrichment analysis, mutations, copy number variations (CNVs) and immune cell infiltration. A total of 275 prognosis-related genes were identified, which were also differentially expressed between ccRCC patients and healthy controls. We then constructed a universal mPS system that depends on the expression status of only 21 of these genes by applying AI-based algorithms. Then, the mPS were validated by another independent cohort and demonstrated to be applicable to ccRCC subsets. Furthermore, a nomogram comprising the mPS score and several independent variables was established and proved to effectively predict ccRCC patient prognosis. Finally, significant differences were identified regarding the pathways, mutated genes, CNVs and tumor-infiltrating immune cells among the subgroups of ccRCC stratified by the mPS system. The AI-based mPS system can provide critical prognostic prediction for ccRCC patients and may be useful to inform treatment and surveillance decisions before initial intervention.

摘要

我们开发并验证了一个新的预测模型,用于预测透明细胞肾细胞癌(ccRCC)患者的总生存期。在这项研究中,我们使用人工智能(AI)算法,包括随机森林和神经网络,来构建一个分子预后评分(mPS)系统。之后,我们通过评估基因集富集分析、突变、拷贝数变异(CNVs)和免疫细胞浸润,来研究 mPS 背后的潜在机制。确定了 275 个与预后相关的基因,这些基因在 ccRCC 患者和健康对照者之间也存在差异表达。然后,我们通过应用基于人工智能的算法,构建了一个仅依赖于其中 21 个基因表达状态的通用 mPS 系统。然后,通过另一个独立的队列验证 mPS,并证明其适用于 ccRCC 亚组。此外,建立了一个包含 mPS 评分和几个独立变量的列线图,并证明其可有效预测 ccRCC 患者的预后。最后,根据 mPS 系统对 ccRCC 患者进行分层,发现了通路、突变基因、CNVs 和肿瘤浸润免疫细胞之间存在显著差异。基于人工智能的 mPS 系统可为 ccRCC 患者提供关键的预后预测,并可能有助于在初始干预前为治疗和监测决策提供信息。

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