ADAMTS8 Expression is a Potential Prognostic Biomarker for Postoperative Metastasis in Lymph Node-Negative Early-Stage Invasive Breast Carcinoma Patients

Yao Li; Xin Yang; Jie Sun; Yangyang Zhao; Qi Zhou; Bin Hua

doi:10.2147/PGPM.S339919

ADAMTS8 Expression is a Potential Prognostic Biomarker for Postoperative Metastasis in Lymph Node-Negative Early-Stage Invasive Breast Carcinoma Patients

Pharmgenomics Pers Med. 2021 Dec 30:14:1701-1713. doi: 10.2147/PGPM.S339919. eCollection 2021.

Authors

Yao Li^#¹, Xin Yang^#¹, Jie Sun², Yangyang Zhao³, Qi Zhou³, Bin Hua¹

Affiliations

¹ 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.
² Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
³ The Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: 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.

Patients and methods: 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 ADAMTS8 expression and prognostic association in our clinical samples (n = 25).

Results: In the discovery cohort (TCGA and GSE20685 datasets), we found that ADAMTS8 tend to be low expression in LN- early-stage BC, and low ADAMTS8 expression was associated with postoperative metastasis and shortened DMFS. Moreover, the above finding was confirmed in the validation cohort (GSE6538 dataset). Lower ADAMTS8 expression was related to poorer prognostic clinical stage and PAM50 subtypes and shorter DMFS. Gene enrichment analysis indicated that ADAMTS8 may be correlated with BC metastasis. qRT-PCR assays of our clinical tumor sample showed that patients with low ADAMTS8 expression seem to be prone to developing metastasis and have a shorter DMFS time.

Conclusion: Our research shows that low ADAMTS8 expression is associated with postoperative metastasis and shortened DMFS in LN- early-stage BC patients, which suggests that ADAMTS8 may be a potential prognostic marker for postoperative metastasis in LN- early-stage BC patients.

Keywords: ADAMTS8; biomarker; distant metastasis-free survival; lymph node-negative early-stage invasive breast carcinoma.

Grants and funding

Beijing Hospital Clinical Research 121 Project(Project Number: BJ-2019-191); Beijing Hospital Project (Project Number: BJ-2021-212).