A Novel Gene Prognostic Signature Based on Differential DNA Methylation in Breast Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34956313", "kind": "science-record", "revision": 4, "content_hash": "sha256:1a09cc29a77c4be2023150d6f8c3591f60e5dfff844ed9f2599ce0bb75f0263f", "created_at": "2026-11-01T17:36:40Z", "updated_at": "2026-11-01T22:05:26Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A Novel Gene Prognostic Signature Based on Differential DNA Methylation in Breast Cancer.", "doi": "10.3389/fgene.2021.742578", "pmid": "34956313", "authors": ["Chunmei Zhu", "Shuyuan Zhang", "Di Liu", "Qingqing Wang", "Ningning Yang", "Zhewen Zheng", "Qiuji Wu", "Yunfeng Zhou"], "journal": "Frontiers in genetics", "year": 2021, "abstract": "Background: DNA methylation played essential roles in regulating gene expression. The impact of DNA methylation status on the occurrence and development of cancers has been well demonstrated. However, little is known about its prognostic role in breast cancer (BC). Materials: The Illumina Human Methylation450 array (450k array) data of BC was downloaded from the UCSC xena database. Transcriptomic data of BC was downloaded from the Cancer Genome Atlas (TCGA) database. Firstly, we used univariate and multivariate Cox regression analysis to screen out independent prognostic CpGs, and then we identified methylation-associated prognosis subgroups by consensus clustering. Next, a methylation prognostic model was developed using multivariate Cox analysis and was validated with the Illumina Human Methylation27 array (27k array) dataset of BC. We then screened out differentially expressed genes (DEGs) between methylation high-risk and low-risk groups and constructed a methylation-based gene prognostic signature. Further, we validated the gene signature with three subgroups of the TCGA-BRCA dataset and an external dataset GSE146558 from the Gene Expression Omnibus (GEO) database. Results: We established a methylation prognostic signature and a methylation-based gene prognostic signature, and there was a close positive correlation between them. The gene prognostic signature involved six genes: IRF2, KCNJ11, ZDHHC9, LRP11, PCMT1, and TMEM70. We verified their expression in mRNA and protein levels in BC. Both methylation and methylation-based gene prognostic signatures showed good prognostic stratification ability. The AUC values of 3-years, 5-years overall survival (OS) were 0.737, 0.744 in the methylation signature and 0.725, 0.715 in the gene signature, respectively. In the validation groups, high-risk patients were confirmed to have poorer OS. The AUC values of 3 years were 0.757, 0.735, 0.733 in the three subgroups of TCGA dataset and 0.635 in GSE146558 dataset. Conclusion: This study revealed the DNA methylation landscape and established promising methylation and methylation-based gene prognostic signatures that could serve as potential prognostic biomarkers and therapeutic targets.", "claims": [{"id": "claim-method", "statement": "Univariate Cox regression analysis was performed to screen out the prognosis-related CpGs of the 560 BC patients.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34956313", "locator": "sections[4] \"Independent Prognostic CpG Loci Screening\" paragraph 2", "quote": "Univariate Cox regression analysis was performed to screen out the prognosis-related CpGs of the 560 BC patients."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34956313", "locator": "sections[23] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study established methylation and methylation-based gene prognostic signatures for breast cancer, with respective 3-year and 5-year overall-survival AUC values of 0.737 and 0.744, and 0.725 and 0.715.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34956313", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The AUC values of 3-years, 5-years overall survival (OS) were 0.737, 0.744 in the methylation signature and 0.725, 0.715 in the gene signature, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study established methylation and methylation-based gene prognostic signatures for breast cancer, with respective 3-year and 5-year overall-survival AUC values of 0.737 and 0.744, and 0.725 and 0.715.", "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:34956313"], "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. 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