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

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35002288", "kind": "science-record", "revision": 5, "content_hash": "sha256:f283cc4ab18269f48f0a7bd9e984c36be13b5fb5ce1c978e70b786e473c07223", "created_at": "2026-11-01T17:36:43Z", "updated_at": "2026-11-01T22:48:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "ADAMTS8 Expression is a Potential Prognostic Biomarker for Postoperative Metastasis in Lymph Node-Negative Early-Stage Invasive Breast Carcinoma Patients.", "doi": "10.2147/PGPM.S339919", "pmid": "35002288", "authors": ["Yao Li", "Xin Yang", "Jie Sun", "Yangyang Zhao", "Qi Zhou", "Bin Hua"], "journal": "Pharmacogenomics and personalized medicine", "year": 2021, "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.\nPATIENTS 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).\nRESULTS: 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.\nCONCLUSION: 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.", "claims": [{"id": "claim-method", "statement": "Kaplan–Meier survival curves were used to compare the high and low expression groups according to the hazard ratio (HR) and log-rank p value.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35002288", "locator": "sections[7] \"Distant Metastasis-Free Survival Analysis\" paragraph 2", "quote": "Kaplan–Meier survival curves were used to compare the high and low expression groups according to the hazard ratio (HR) and log-rank p value."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Transcriptome and clinical data from BC patients were downloaded from TCGA (https://portal.gdc.cancer.gov/), and the microarray gene expression profiles and clinical data were retrieved from the GEO (GSE20685, GSE6532) (https://www.ncbi.nlm.nih.gov/gds) database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35002288", "locator": "sections[3] \"Data Extraction\" paragraph 2", "quote": "Transcriptome and clinical data from BC patients were downloaded from TCGA (https://portal.gdc.cancer.gov/), and the microarray gene expression profiles and clinical data were retrieved from the GEO (GSE20685, GSE6532) (https://www.ncbi.nlm.nih.gov/gds) database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We found that low ADAMTS8 expression was a high risk factor for postoperative metastasis in both discovery datasets (TCGA: HR = 5.637 [1.915–16.595], p = 0.002; GSE20685: HR = 14.550 [1.853–114.230], p = 0.011).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35002288", "locator": "sections[13] \"Identification of Candidate Gene in the Discovery Cohort\" paragraph 5", "quote": "We found that low ADAMTS8 expression was a high risk factor for postoperative metastasis in both discovery datasets (TCGA: HR = 5.637 [1.915–16.595], p = 0.002; GSE20685: HR = 14.550 [1.853–114.230], p = 0.011)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We found that low ADAMTS8 expression was a high risk factor for postoperative metastasis in both discovery datasets (TCGA: HR = 5.637 [1.915–16.595], p = 0.002; GSE20685: HR = 14.550 [1.853–114.230], p = 0.011).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35002288"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE20685"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE20685"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35002288", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/PGPM.S339919", "sha256": 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