Radiogenomic-based multiomic analysis reveals imaging intratumor heterogeneity phenotypes and therapeutic targets.
Radiogenomic-based multiomic analysis reveals imaging intratumor heterogeneity phenotypes and therapeutic targets.
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DOI：
10.1126/sciadv.adf0837
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发表时间：
2023-10-06
期刊：
影响因子：
13.6
通讯作者：
Jiang, Yi-Zhou
中科院分区：
文献类型：
--
作者：
Su, Guan-Hua;Xiao, Yi;You, Chao;Zheng, Ren-Cheng;Zhao, Shen;Sun, Shi-Yun;Zhou, Jia-Yin;Lin, Lu-Yi;Wang, He;Shao, Zhi-Ming;Gu, Ya-Jia;Jiang, Yi-Zhou
瘤内异质性（ITH）深刻影响治疗反应和临床结局。然而，基于基因组测序或病理切片评估ITH的广泛方法依赖于有限的组织样本，可能由于潜在的采样偏差而导致不准确。使用一个新建立的多中心乳腺癌放射多组学数据集（n = 1474）包含放射组学特征提取动态对比增强磁共振图像，我们制定了一个非侵入性放射组学方法，有效地调查ITH。成像ITH（IITH）与基因组和病理ITH相关，独立预测乳腺癌的不良预后。通过多组学分析，我们确定了高IITH肿瘤中激活的致癌通路和代谢失调。综合代谢组学和转录组学分析强调了铁凋亡作为高IITH肿瘤的脆弱性和潜在治疗靶点。总的来说，这项工作强调了放射组学在捕获ITH方面的优势。此外，我们提供了深入了解IITH的生物学基础，并提出了IITH升高的乳腺癌的治疗靶点。一项大规模多中心放射多组学研究解码了肿瘤内异质性成像并揭示了其生物学意义。
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. A large-scale multicenter radio-multiomic study decodes imaging intratumor heterogeneity and unravels its biological significance.
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影响因子：
64.8
作者：
Greaves, Mel;Maley, Carlo C.
通讯作者：
Maley, Carlo C.
影响因子：
14.3
作者：
Jiang, Lin;You, Chao;Xiao, Yi;Wang, He;Su, Guan-Hua;Xia, Bing-Qing;Zheng, Ren-Cheng;Zhang, Dan-Dan;Jiang, Yi-Zhou;Gu, Ya-Jia;Shao, Zhi-Ming
通讯作者：
Shao, Zhi-Ming
DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.4
作者：
Clark, Kenneth;Vendt, Bruce;Prior, Fred
通讯作者：
Prior, Fred
影响因子：
28.2
作者：
Greaves M
通讯作者：
Greaves M