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Radiogenomic-based multiomic analysis reveals imaging intratumor heterogeneity phenotypes and therapeutic targets.

ABSTRACT: 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.

SUBMITTER: Su GH

PROVIDER: S-EPMC10558123 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Radiogenomic-based multiomic analysis reveals imaging intratumor heterogeneity phenotypes and therapeutic targets.

Su Guan-Hua GH Xiao Yi Y You Chao C Zheng Ren-Cheng RC Zhao Shen S Sun Shi-Yun SY Zhou Jia-Yin JY Lin Lu-Yi LY Wang He H Shao Zhi-Ming ZM Gu Ya-Jia YJ Jiang Yi-Zhou YZ

Science advances 20231006 40

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 (<i>n</i> = 1474) encompassing radiomic features extracted from dynamic contrast-enhanced magnetic resonance images, we formulated ...[more]

PMID: 37801493

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Dataset Information

Radiogenomic-based multiomic analysis reveals imaging intratumor heterogeneity phenotypes and therapeutic targets.

Publications

Radiogenomic-based multiomic analysis reveals imaging intratumor heterogeneity phenotypes and therapeutic targets.

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