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 , lymph node-negative early-stage invasive breast carcinoma, distant metastasis-free survival, biomarker