Identification and validation of a novel prognostic signature based on transcription factors in breast cancer by bioinformatics analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35694087", "kind": "science-record", "revision": 3, "content_hash": "sha256:18bd3d29f74b3795a9689ab4b82724f9b92348e7a7d9842926b31cd05be00960", "created_at": "2026-11-01T18:14:40Z", "updated_at": "2026-11-01T21:28:06Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of a novel prognostic signature based on transcription factors in breast cancer by bioinformatics analysis.", "doi": "10.21037/gs-22-267", "pmid": "35694087", "authors": ["Yingmei Yang", "Zhaoyun Li", "Qianyi Zhong", "Lei Zhao", "Yichao Wang", "Hongbo Chi"], "journal": "Gland surgery", "year": 2022, "abstract": "Background: Breast cancer (BRCA) is the leading cause of cancer mortality among women, and it is associated with many tumor suppressors and oncogenes. There is increasing evidence that transcription factors (TFs) play vital roles in human malignancies, but TFs-based biomarkers for BRCA prognosis were still rare and necessary. This study sought to develop and validate a prognostic model based on TFs for BRCA patients.\nMethods: Differentially expressed TFs were screened from 1,109 BRCA and 113 non-tumor samples downloaded from The Cancer Genome Atlas (TCGA). Univariate Cox regression analysis was used to identify TFs associated with overall survival (OS) of BRCA, and multivariate Cox regression analysis was performed to establish the optimal risk model. The predictive value of the TF model was established using TCGA database and validated using a Gene Expression Omnibus (GEO) data set (GSE20685). A gene set enrichment analysis was conducted to identify the enriched signaling pathways in high-risk and low-risk BRCA patients. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the TF target genes were also conducted separately.\nResults: A total of 394 differentially expressed TFs were screened. A 9-TF prognostic model, comprising PAX7, POU3F2, ZIC2, WT1, ALX4, FOXJ1, SPIB, LEF1 and NFE2, was constructed and validated. Compared to those in the low-risk group, patients in the high-risk group had worse clinical outcomes (P<0.001). The areas under the curve of the prognostic model for 5-year OS were 0.722 in the training cohort and 0.651 in the testing cohort. Additionally, the risk score was an independent prediction indicator for BRCA patients both in the training cohort (HR =1.757, P<0.001) and testing cohort (HR =1.401, P=0.001). It was associated with various cancer signaling pathways. Ultimately, 9 overlapping target genes were predicted by 3 prediction nomograms. The GO and KEGG enrichment analyses of these target genes suggested that the TFs in the model may regulate the activation of some classical tumor signaling pathways to control the progression of BRCA through these target genes.\nConclusions: Our study developed and validated a novel prognostic TF model that can effectively predict 5-year OS for BRCA patients.", "claims": [{"id": "claim-method", "statement": "Univariate Cox regression analysis was used to identify TFs associated with overall survival (OS) of BRCA, and multivariate Cox regression analysis was performed to establish the optimal risk model.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35694087", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Univariate Cox regression analysis was used to identify TFs associated with overall survival (OS) of BRCA, and multivariate Cox regression analysis was performed to establish the optimal risk model."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Differentially expressed TFs were screened from 1,109 BRCA and 113 non-tumor samples downloaded from The Cancer Genome Atlas (TCGA).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35694087", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Differentially expressed TFs were screened from 1,109 BRCA and 113 non-tumor samples downloaded from The Cancer Genome Atlas (TCGA)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A 9-TF prognostic model was constructed and validated for predicting 5-year overall survival in BRCA patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35694087", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A 9-TF prognostic model, comprising PAX7, POU3F2, ZIC2, WT1, ALX4, FOXJ1, SPIB, LEF1 and NFE2, was constructed and validated."}, {"asset": "source:pmid:35694087", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Our study developed and validated a novel prognostic TF model that can effectively predict 5-year OS for BRCA patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A 9-TF prognostic model was constructed and validated for predicting 5-year overall survival in BRCA patients.", "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:35694087"], "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:35694087", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/gs-22-267", "sha256": 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