Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineerings, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Medical Statistics Office, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J Gene Med. 2024 Jan;26(1):e3604. doi: 10.1002/jgm.3604. Epub 2023 Oct 25.
Breast cancer (BC) is the most common cancer among women worldwide and a leading cause of cancer-associated deaths among women. However, there is a lack of accurate prognostic biomarkers for BC. In the present study, we aimed to identify a genomic instability (GI)-associated microRNA signature as a novel potential prognostic biomarker in BC.
We performed an integrative analysis to investigate the relationship between GI and BC and identify GI-associated microRNAs (miRNAs). Subsequently, we conducted a discovery and validation study using multicenter cohorts. The GI-associated miRNA signature was developed in the discovery cohort and independently validated in internal and external cohorts.
GI-associated miRNAs expression in BC showed heterogeneity and was significantly correlated with BC prognosis. We identified a GI-associated two-miRNA signature (miR-105-5p and miR-767-5p), termed GI2miR, that stratified BC patients into high-risk and low-risk groups with significantly different clinical outcomes (log-rank p = 0.027) in The Cancer Genome Atlas (TCGA) discovery cohort (n = 763). The prognostic value of GI2miR was further validated in internal TCGA validation cohort (n = 253) (log-rank p = 0.035) and independent GSE22216 cohort (n = 210) (log-rank p = 0.036). The GI2miR demonstrated independent prognostic value in multivariate Cox proportional hazard regression analyses and stratification analysis.
We have developed a novel prognostic signature based on GI-associated two miRNAs for BC, which may lay the foundation for BC to improve prognosis prediction.
乳腺癌（BC）是全世界女性中最常见的癌症，也是女性癌症相关死亡的主要原因。然而，BC 缺乏准确的预后生物标志物。本研究旨在鉴定与基因组不稳定性（GI）相关的 microRNA 特征，作为 BC 潜在的新型预后生物标志物。
我们进行了综合分析，以研究 GI 与 BC 之间的关系并鉴定与 GI 相关的 microRNAs（miRNAs）。随后，我们使用多中心队列进行了发现和验证研究。在发现队列中开发 GI 相关 miRNA 特征，并在内部和外部队列中独立验证。
BC 中 GI 相关 miRNA 的表达具有异质性，并且与 BC 预后显著相关。我们确定了一个 GI 相关的两个 miRNA 特征（miR-105-5p 和 miR-767-5p），称为 GI2miR，它将 TCGA 发现队列（n=763）中的 BC 患者分为高危和低危组，临床结局有显著差异（对数秩检验 p=0.027）。GI2miR 的预后价值在 TCGA 内部验证队列（n=253）（对数秩检验 p=0.035）和独立的 GSE22216 队列（n=210）（对数秩检验 p=0.036）中得到了进一步验证。在多变量 Cox 比例风险回归分析和分层分析中，GI2miR 显示出独立的预后价值。
我们基于与 GI 相关的两个 miRNA 为 BC 开发了一种新的预后特征，这可能为 BC 改善预后预测奠定基础。
