血浆 cfDNA 中的启动子谱表现出预测乳腺癌患者新辅助化疗疗效的潜在效用。
Promoter profiles in plasma CfDNA exhibits a potential utility of predicting the efficacy of neoadjuvant chemotherapy in breast cancer patients.
机构信息
Institute of Antibody Engineering, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
Department of Pathology, The First People's Hospital of Foshan, Foshan, China.
出版信息
Breast Cancer Res. 2024 Jul 4;26(1):112. doi: 10.1186/s13058-024-01860-3.
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.
背景
乳腺组织活检中的基因表达谱包含与化疗疗效相关的信息。来源于原始组织的无细胞 DNA（cfDNA）中携带基因表达信息的启动子谱，可能被用作预测乳腺癌新辅助化疗反应的非侵入性生物标志物。在这项研究中，评估了血浆 cfDNA 中启动子谱作为一种新的临床模型，用于无创预测乳腺癌新辅助化疗疗效的可行性。
方法
首先，分析了 94 例接受新辅助化疗的乳腺癌患者（pCR=31 例，非 pCR=63 例）治疗前血浆 cfDNA 样本中的全染色质（5Mb 窗口）、亚区室和启动子谱，并为预测乳腺癌新辅助化疗的疗效开发了分类器。进一步分析了 30 例患者（pCR=8 例，非 pCR=22 例）在新辅助化疗过程中连续 cfDNA 样本中的启动子谱变化，以探讨 cfDNA 启动子谱变化作为一种新的潜在生物标志物预测治疗疗效的潜在益处。
结果
结果显示，与新辅助化疗前非 pCR 患者相比，pCR 患者血浆 cfDNA 中的启动子谱明显不同。基于随机森林模型中启动子谱的分类器产生了最大的曲线下面积为 0.980（95%CI：0.978-0.983）。新辅助化疗后，与非 pCR 患者相比，在 pCR 患者连续 cfDNA 样本中观察到 332 个具有显著差异的启动子谱变化的基因，其功能与治疗反应密切相关。
结论
这些结果表明，血浆 cfDNA 中的启动子谱可能是一种强大的、无创的工具，可用于预测治疗前乳腺癌新辅助化疗患者的疗效，治疗中的 cfDNA 启动子谱对预测治疗疗效具有潜在的益处。
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