血浆 CfDNA 的启动子图谱可用于预测乳腺癌患者新辅助化疗的疗效。

IF 7.4 1区 医学 Q1 Medicine
Xu Yang, Qing Liu, Zhiwei Guo, Xuexi Yang, Kun Li, Bowei Han, Min Zhang, Minying Sun, Limin Huang, Gengxi Cai, Yingsong Wu
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引用次数: 0

摘要

背景乳腺组织活检样本中的基因表达谱包含与化疗疗效相关的信息。携带原始组织基因表达信息的无细胞DNA(cfDNA)中的启动子图谱作为一种非侵入性生物标志物,可用于预测乳腺癌患者对新辅助化疗的反应。本研究评估了将血浆 cfDNA 中的启动子图谱作为一种新型临床模型来无创预测乳腺癌新辅助化疗疗效的可行性:首先,分析了新辅助化疗前94例乳腺癌患者(pCR=31例与非pCR=63例)血浆cfDNA样本中的全染色质(5Mb窗口)、亚区和启动子图谱,然后开发了预测乳腺癌新辅助化疗疗效的分类器。此外,研究人员还分析了新辅助化疗期间30例患者(pCR=8例与非pCR=22例)的连续cfDNA样本的启动子图谱变化,以探索cfDNA启动子图谱变化作为预测疗效的新型潜在生物标记物的潜在益处:结果表明,在新辅助化疗前,pCR患者血浆cfDNA的启动子谱与非pCR患者相比明显不同。随机森林模型中基于启动子图谱的分类器产生的曲线下面积最大,为0.980(95% CI:0.978-0.983)。新辅助化疗后,与非克罗恩患者相比,在克罗恩患者的连续cfDNA样本中观察到332个基因的启动子谱发生了显著差异变化,其功能与治疗反应密切相关:这些结果表明,血浆中cfDNA的启动子图谱可能是预测乳腺癌患者治疗前新辅助化疗疗效的有力、非侵入性工具,而治疗中的cfDNA启动子图谱对预测疗效也有潜在的益处。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Promoter profiles in plasma CfDNA exhibits a potential utility of predicting the efficacy of neoadjuvant chemotherapy in breast cancer patients.

Background: Gene expression profiles in breast tissue biopsies contain information related to chemotherapy efficacy. The promoter profiles in cell-free DNA (cfDNA) carrying gene expression information of the original tissues may be used to predict the response to neoadjuvant chemotherapy in breast cancer as a non-invasive biomarker. In this study, the feasibility of the promoter profiles in plasma cfDNA was evaluated as a novel clinical model for noninvasively predicting the efficacy of neoadjuvant chemotherapy in breast cancer.

Method: First of all, global chromatin (5 Mb windows), sub-compartments and promoter profiles in plasma cfDNA samples from 94 patients with breast cancer before neoadjuvant chemotherapy (pCR = 31 vs. non-pCR = 63) were analyzed, and then classifiers were developed for predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Further, the promoter profile changes in sequential cfDNA samples from 30 patients (pCR = 8 vs. non-pCR = 22) during neoadjuvant chemotherapy were analyzed to explore the potential benefits of cfDNA promoter profile changes as a novel potential biomarker for predicting the treatment efficacy.

Results: The results showed significantly distinct promoter profile in plasma cfDNA of pCR patients compared with non-pCR patients before neoadjuvant chemotherapy. The classifier based on promoter profiles in a Random Forest model produced the largest area under the curve of 0.980 (95% CI: 0.978-0.983). After neoadjuvant chemotherapy, 332 genes with significantly differential promoter profile changes in sequential cfDNA samples of pCR patients was observed, compared with non-pCR patients, and their functions were closely related to treatment response.

Conclusion: These results suggest that promoter profiles in plasma cfDNA may be a powerful, non-invasive tool for predicting the efficacy of neoadjuvant chemotherapy breast cancer patients before treatment, and the on-treatment cfDNA promoter profiles have potential benefits for predicting the treatment efficacy.

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来源期刊
CiteScore
12.00
自引率
0.00%
发文量
76
审稿时长
12 weeks
期刊介绍: Breast Cancer Research, an international, peer-reviewed online journal, publishes original research, reviews, editorials, and reports. It features open-access research articles of exceptional interest across all areas of biology and medicine relevant to breast cancer. This includes normal mammary gland biology, with a special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition to basic research, the journal covers preclinical, translational, and clinical studies with a biological basis, including Phase I and Phase II trials.
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