乳腺癌
放射基因组学
无线电技术
转录组
表型
计算生物学
肿瘤异质性
磁共振成像
医学
癌症
癌症研究
生物
内科学
基因
遗传学
基因表达
放射科
作者
Guan-Hua Su,Yi Xiao,Chao You,Rencheng Zheng,Shen Zhao,Shiyun Sun,J Zhou,Luyi Lin,He Wang,Zhi‐Ming Shao,Yajia Gu,Yi‐Zhou Jiang
出处
期刊:Science Advances
[American Association for the Advancement of Science]
日期:2023-10-06
卷期号:9 (40)
被引量:39
标识
DOI:10.1126/sciadv.adf0837
摘要
Intratumor heterogeneity (ITH) profoundly affects therapeutic responses and clinical outcomes. However, the widespread methods for assessing ITH based on genomic sequencing or pathological slides, which rely on limited tissue samples, may lead to inaccuracies due to potential sampling biases. Using a newly established multicenter breast cancer radio-multiomic dataset ( n = 1474) encompassing radiomic features extracted from dynamic contrast–enhanced magnetic resonance images, we formulated a noninvasive radiomics methodology to effectively investigate ITH. Imaging ITH (IITH) was associated with genomic and pathological ITH, predicting poor prognosis independently in breast cancer. Through multiomic analysis, we identified activated oncogenic pathways and metabolic dysregulation in high-IITH tumors. Integrated metabolomic and transcriptomic analyses highlighted ferroptosis as a vulnerability and potential therapeutic target of high-IITH tumors. Collectively, this work emphasizes the superiority of radiomics in capturing ITH. Furthermore, we provide insights into the biological basis of IITH and propose therapeutic targets for breast cancers with elevated IITH.
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