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机器学习磁共振成像放射组学预测乳腺癌患者手术后无复发生存率及 LncRNAs 的相关性:多中心队列研究。

Machine learning radiomics of magnetic resonance imaging predicts recurrence-free survival after surgery and correlation of LncRNAs in patients with breast cancer: a multicenter cohort study.

机构信息

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Medical Oncology, Breast Tumor Center, Phase I Clinical Trial Centre, Artificial Intelligence Laboratory, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang West Road, 510120, Guangzhou, People's Republic of China.

Faculty of Medicine, Macau University of Science and Technology, Taipa, Macao, People's Republic of China.

出版信息

Breast Cancer Res. 2023 Nov 1;25(1):132. doi: 10.1186/s13058-023-01688-3.

Abstract

BACKGROUND

Several studies have indicated that magnetic resonance imaging radiomics can predict survival in patients with breast cancer, but the potential biological underpinning remains indistinct. Herein, we aim to develop an interpretable deep-learning-based network for classifying recurrence risk and revealing the potential biological mechanisms.

METHODS

In this multicenter study, 1113 nonmetastatic invasive breast cancer patients were included, and were divided into the training cohort (n = 698), the validation cohort (n = 171), and the testing cohort (n = 244). The Radiomic DeepSurv Net (RDeepNet) model was constructed using the Cox proportional hazards deep neural network DeepSurv for predicting individual recurrence risk. RNA-sequencing was performed to explore the association between radiomics and tumor microenvironment. Correlation and variance analyses were conducted to examine changes of radiomics among patients with different therapeutic responses and after neoadjuvant chemotherapy. The association and quantitative relation of radiomics and epigenetic molecular characteristics were further analyzed to reveal the mechanisms of radiomics.

RESULTS

The RDeepNet model showed a significant association with recurrence-free survival (RFS) (HR 0.03, 95% CI 0.02-0.06, P < 0.001) and achieved AUCs of 0.98, 0.94, and 0.92 for 1-, 2-, and 3-year RFS, respectively. In the validation and testing cohorts, the RDeepNet model could also clarify patients into high- and low-risk groups, and demonstrated AUCs of 0.91 and 0.94 for 3-year RFS, respectively. Radiomic features displayed differential expression between the two risk groups. Furthermore, the generalizability of RDeepNet model was confirmed across different molecular subtypes and patient populations with different therapy regimens (All P < 0.001). The study also identified variations in radiomic features among patients with diverse therapeutic responses and after neoadjuvant chemotherapy. Importantly, a significant correlation between radiomics and long non-coding RNAs (lncRNAs) was discovered. A key lncRNA was found to be noninvasively quantified by a deep learning-based radiomics prediction model with AUCs of 0.79 in the training cohort and 0.77 in the testing cohort.

CONCLUSIONS

This study demonstrates that machine learning radiomics of MRI can effectively predict RFS after surgery in patients with breast cancer, and highlights the feasibility of non-invasive quantification of lncRNAs using radiomics, which indicates the potential of radiomics in guiding treatment decisions.

摘要

背景

多项研究表明,磁共振成像放射组学可以预测乳腺癌患者的生存情况,但潜在的生物学基础仍不明确。在此,我们旨在开发一种可解释的基于深度学习的网络,用于分类复发风险并揭示潜在的生物学机制。

方法

在这项多中心研究中,纳入了 1113 例非转移性浸润性乳腺癌患者,分为训练队列(n=698)、验证队列(n=171)和测试队列(n=244)。使用 Cox 比例风险深度学习网络 DeepSurv 构建放射组学深度生存网络(RDeepNet)模型,用于预测个体复发风险。进行 RNA 测序以探索放射组学与肿瘤微环境之间的关联。进行相关性和方差分析,以检测不同治疗反应和新辅助化疗后患者放射组学的变化。进一步分析放射组学与表观遗传分子特征的关联和定量关系,以揭示放射组学的机制。

结果

RDeepNet 模型与无复发生存率(RFS)显著相关(HR 0.03,95%CI 0.02-0.06,P<0.001),并分别获得 1 年、2 年和 3 年 RFS 的 AUC 为 0.98、0.94 和 0.92。在验证和测试队列中,RDeepNet 模型也可以将患者分为高风险和低风险组,并且分别在 3 年 RFS 中获得 AUC 为 0.91 和 0.94。放射组学特征在两个风险组之间显示出差异表达。此外,RDeepNet 模型在不同分子亚型和不同治疗方案的患者人群中具有很好的泛化能力(均 P<0.001)。该研究还确定了不同治疗反应和新辅助化疗后患者放射组学特征的变化。重要的是,发现放射组学与长链非编码 RNA(lncRNA)之间存在显著相关性。基于深度学习的放射组学预测模型可以无创定量检测到一个关键 lncRNA,在训练队列中的 AUC 为 0.79,在测试队列中的 AUC 为 0.77。

结论

本研究表明,磁共振成像放射组学机器学习可有效预测乳腺癌患者手术后的 RFS,并强调了使用放射组学进行 lncRNA 无创定量的可行性,这表明放射组学在指导治疗决策方面具有潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a6/10619251/01eef585ce8d/13058_2023_1688_Fig1_HTML.jpg

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