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通过综合基因组,转录组和循环瘤DNA分析,解开乳腺癌对新辅助化疗的反应

Menghao Dong¹, Jian Chen¹, Nannan Lu¹

¹Department of Clinical Oncology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, No. 17 Lujiang Road, Luyang District, Hefei, Anhui, 230001, China.

Breast cancer research : BCR

|May 1, 2025

概括

这项研究确定了关键的基因突变和分子途径,可以预测乳腺癌对新辅助化疗 (NAC) 的反应. 早期检测循环瘤DNA (ctDNA) 和特定基线突变对于分层患者和改善生存结果至关重要.

科学领域:

在瘤学瘤学.
基因组学就是基因组学.
分子生物学分子生物学

背景情况:

新辅助化疗 (NAC) 是乳腺癌 (BC) 的标准,但其反应机制和预后因素需要进一步阐明.
了解NAC反应的分子基础对于改善患者分层和治疗结果在II/IIIBC阶段至关重要.

研究的目的:

确定可预测病理完整反应 (pCR) 和乳腺癌患者接受NAC的存活率的分子生物标志物.
描述与NAC反应和预后相关的基因组和转录组变异.

主要方法:

在NAC之前和之后的73名II/III期BC患者的瘤组织的多组分析 (基因组,转录组).
在NAC期间在三个时间点进行长度血循环瘤DNA (ctDNA) 分析.
分子发现与pCR和患者生存结果的相关性.

主要成果:

九个基线突变 (例如,DNHD1,PLEC) 和与pCR相关的HIPPO通路变化.
响应性瘤显示免疫激活和改变PI3K-Akt/AGE-RAGE通路;非pCR瘤减少了免疫活性.
在NAC期间/之后无法检测到的ctDNA预测了疗效和改善的生存率;USH2A突变和高NHSL1表达与较差的生存率有关.

结论:

综合的多omics分析揭示了用于预测NAC反应和乳腺癌生存的新生物标志物.
使用这些生物标志物的早期瘤评估可以显著改善患者分层和NAC治疗的预后.

关键词:

乳腺癌乳腺癌乳腺癌分子生物标志物分子生物标志物新辅助化学疗法新辅助化学疗法病理完整反应的病理完整反应

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