一种利用转录组数据表征癌症药物诱导的衰老效应的计算框架。

A Computational Framework to Characterize the Cancer Drug Induced Effect on Aging Using Transcriptomic Data.

作者信息

Zhao Yueshan, Wang Yue, Yang Da, Suh Kangho, Zhang Min

机构信息

Center for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, United States.

UPMC Hillman Cancer Institute, University of Pittsburgh, Pittsburgh, PA, United States.

出版信息

Front Pharmacol. 2022 Jun 29;13:906429. doi: 10.3389/fphar.2022.906429. eCollection 2022.

DOI:10.3389/fphar.2022.906429

PMID:35847024

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9277350/

Abstract

Cancer treatments such as chemotherapies may change or accelerate aging trajectories in cancer patients. Emerging evidence has shown that "omics" data can be used to study molecular changes of the aging process. Here, we integrated the drug-induced and normal aging transcriptomic data to computationally characterize the potential cancer drug-induced aging process in patients. Our analyses demonstrated that the aging-associated gene expression in the GTEx dataset can recapitulate the well-established aging hallmarks. We next characterized the drug-induced transcriptomic changes of 28 FDA approved cancer drugs in brain, kidney, muscle, and adipose tissues. Further drug-aging interaction analysis identified 34 potential drug regulated aging events. Those events include aging accelerating effects of vandetanib (Caprelsa®) and dasatinib (Sprycel®) in brain and muscle, respectively. Our result also demonstrated aging protective effect of vorinostat (Zolinza®), everolimus (Afinitor®), and bosutinib (Bosulif®) in brain.

摘要

化疗等癌症治疗方法可能会改变或加速癌症患者的衰老轨迹。新出现的证据表明，“组学”数据可用于研究衰老过程的分子变化。在此，我们整合了药物诱导和正常衰老的转录组数据，以通过计算表征患者潜在的癌症药物诱导衰老过程。我们的分析表明，GTEx数据集中与衰老相关的基因表达可以概括已确立的衰老特征。接下来，我们表征了28种美国食品药品监督管理局（FDA）批准的癌症药物在脑、肾、肌肉和脂肪组织中的药物诱导转录组变化。进一步的药物 - 衰老相互作用分析确定了34个潜在的药物调节衰老事件。这些事件包括凡德他尼（Caprelsa®）和达沙替尼（Sprycel®）分别在脑和肌肉中的衰老加速作用。我们的结果还表明伏立诺他（Zolinza®）、依维莫司（Afinitor®）和博舒替尼（Bosulif®）在脑中具有衰老保护作用。