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线粒体调控通路在透明细胞肾细胞癌临床应用中的潜在价值:基于机器学习的研究。

Potential value of mitochondrial regulatory pathways in the clinical application of clear cell renal cell carcinoma: a machine learning-based study.

机构信息

Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.

Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.

出版信息

J Cancer Res Clin Oncol. 2023 Dec;149(19):17015-17026. doi: 10.1007/s00432-023-05393-8. Epub 2023 Sep 25.

Abstract

BACKGROUND

Renal clear cell carcinoma (RCC) is a common cancer in urinary system with increasing incidence. At present, targeted therapy and immunotherapy are the main therapeutic programs in clinical therapy. To develop novel drugs and provide new ideas for clinical therapy, the identification of potential ccRCC subtypes and potential target genes or pathways has become a current research focus.

AIM

The aim of this study was to explore the underlying mechanisms of mitochondrial function in ccRCC. This regulatory pathway is closely related to tumor development and metastasis in ccRCC patients, and their abnormal changes may affect the prognosis of cancer patients. Therefore, we decided to construct a prognostic model of ccRCC patients based on mitochondrial regulatory genes, aiming to provide new methods and ideas for clinical therapy.

RESULT

The 5-year survival prediction model based on iterative LASSO reached 0.746, and the cox model based on coxph reached C-index = 0.77, integrated c/D AUC = 0.61, and integrated brier score = 0.14. The rsf model based on randomForestSRC was built with C-index = 0.82, integrated c/D AUC = 0.69, and integrated brier score = 0.11. The results show that mitochondrial regulatory pathway is a potential target pathway for clinical therapy of ccRCC, which can provide guidelines for clinical targeted therapy, immunotherapy and other first-line therapy.

摘要

背景

肾透明细胞癌(RCC)是泌尿系统常见的癌症,发病率呈上升趋势。目前,靶向治疗和免疫治疗是临床治疗的主要方案。为了开发新的药物并为临床治疗提供新的思路,鉴定潜在的 ccRCC 亚型和潜在的靶基因或途径已成为当前的研究热点。

目的

本研究旨在探讨线粒体功能在 ccRCC 中的潜在机制。该调控途径与 ccRCC 患者的肿瘤发生和转移密切相关,其异常变化可能影响癌症患者的预后。因此,我们决定基于线粒体调控基因构建 ccRCC 患者的预后模型,旨在为临床治疗提供新的方法和思路。

结果

基于迭代 LASSO 的 5 年生存预测模型达到 0.746,基于 coxph 的 cox 模型达到 C-index=0.77,综合 c/D AUC=0.61,综合 brier 得分=0.14。基于 randomForestSRC 的 rsf 模型的 C-index=0.82,综合 c/D AUC=0.69,综合 brier 得分=0.11。结果表明,线粒体调控途径是 ccRCC 临床治疗的潜在靶点途径,可为临床靶向治疗、免疫治疗等一线治疗提供指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea5/11798179/6998c2766073/432_2023_5393_Fig1_HTML.jpg

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