Li Yao, Yang Xin, Sun Jie, Zhao Yangyang, Zhou Qi, Hua Bin
Breast Center, Department of Thyroid-Breast-Hernia Surgery, Department of General Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Pharmgenomics Pers Med. 2021 Dec 30;14:1701-1713. doi: 10.2147/PGPM.S339919. eCollection 2021.
Invasive breast carcinoma (BC) is the most common malignant breast tumor. Most lymph node-negative (LN) early-stage BC patients usually have a good prognosis, but 7% of patients still develop metastasis after surgery. It is not yet clear how to screen candidates with poorer prognosis in LN- early-stage patients, so that they can receive intensive therapy. Hence, we expect to identify a prognostic biomarker to assess postoperative metastasis in LN- early-stage BC patients.
Screening and verifying of candidate genes by gene expression profiling of LN- early-stage BC samples (n = 640) from 3 independent public datasets. Univariable and multivariable Cox regression analyses showed the relation between the candidate genes and postoperative metastasis. Distant metastasis-free survival (DMFS) analysis was performed to examine the prognostic significance. Quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed to examine expression and prognostic association in our clinical samples (n = 25).
In the discovery cohort (TCGA and GSE20685 datasets), we found that tend to be low expression in LN- early-stage BC, and low expression was associated with postoperative metastasis and shortened DMFS. Moreover, the above finding was confirmed in the validation cohort (GSE6538 dataset). Lower expression was related to poorer prognostic clinical stage and PAM50 subtypes and shorter DMFS. Gene enrichment analysis indicated that may be correlated with BC metastasis. qRT-PCR assays of our clinical tumor sample showed that patients with low expression seem to be prone to developing metastasis and have a shorter DMFS time.
Our research shows that low expression is associated with postoperative metastasis and shortened DMFS in LN- early-stage BC patients, which suggests that may be a potential prognostic marker for postoperative metastasis in LN- early-stage BC patients.
浸润性乳腺癌(BC)是最常见的乳腺恶性肿瘤。大多数淋巴结阴性(LN)的早期BC患者通常预后良好,但7%的患者术后仍会发生转移。目前尚不清楚如何筛选LN早期患者中预后较差的候选者,以便他们能够接受强化治疗。因此,我们期望鉴定一种预后生物标志物,以评估LN早期BC患者术后的转移情况。
通过对来自3个独立公共数据集的LN早期BC样本(n = 640)进行基因表达谱分析,筛选并验证候选基因。单变量和多变量Cox回归分析显示候选基因与术后转移之间的关系。进行无远处转移生存期(DMFS)分析以检验预后意义。采用定量实时聚合酶链反应(qRT-PCR)检测我们临床样本(n = 25)中的表达及预后相关性。
在发现队列(TCGA和GSE20685数据集)中,我们发现 在LN早期BC中往往低表达,低表达与术后转移及缩短的DMFS相关。此外,上述发现在验证队列(GSE6538数据集)中得到证实。较低的 表达与较差的预后临床分期和PAM50亚型以及较短的DMFS相关。基因富集分析表明 可能与BC转移相关。我们临床肿瘤样本的qRT-PCR检测显示, 表达低的患者似乎更容易发生转移且DMFS时间较短。
我们的研究表明,低 表达与LN早期BC患者术后转移及缩短的DMFS相关,这表明 可能是LN早期BC患者术后转移的潜在预后标志物。