Identification of potential genes related to breast cancer brain metastasis in breast cancer patients.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34541602", "kind": "science-record", "revision": 8, "content_hash": "sha256:3a4ac1ff0606f5a828aeaf1d0438b536631c036b21822a1be0f1804fe7ebec27", "created_at": "2026-11-01T15:41:53Z", "updated_at": "2026-11-01T22:47:33Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of potential genes related to breast cancer brain metastasis in breast cancer patients.", "doi": "10.1042/BSR20211615", "pmid": "34541602", "authors": ["Lijian Zhang", "Luxuan Wang", "Hua Yang", "Chunhui Li", "Chuan Fang"], "journal": "Bioscience reports", "year": 2021, "abstract": "Brain metastases (BMs) usually develop in breast cancer (BC) patients. Thus, the molecular mechanisms of breast cancer brain metastasis (BCBM) are of great importance in designing therapeutic strategies to treat or prevent BCBM. The present study attempted to identify novel diagnostic and prognostic biomarkers of BCBM. Two datasets (GSE125989 and GSE100534) were obtained from the Gene Expression Omnibus (GEO) database to find differentially expressed genes (DEGs) in cases of BC with and without brain metastasis (BM). A total of 146 overlapping DEGs, including 103 up-regulated and 43 down-regulated genes, were identified. Functional enrichment analysis showed that these DEGs were mainly enriched for functions including extracellular matrix (ECM) organization and collagen catabolic fibril organization. Using protein-protein interaction (PPI) and principal component analysis (PCA) analysis, we identified ten key genes, including LAMA4, COL1A1, COL5A2, COL3A1, COL4A1, COL5A1, COL5A3, COL6A3, COL6A2, and COL6A1. Additionally, COL5A1, COL4A1, COL1A1, COL6A1, COL6A2, and COL6A3 were significantly associated with the overall survival of BC patients. Furthermore, COL6A3, COL5A1, and COL4A1 were potentially correlated with BCBM in human epidermal growth factor 2 (HER2) expression. Additionally, the miR-29 family might participate in the process of metastasis by modulating the cancer microenvironment. Based on datasets in the GEO database, several DEGs have been identified as playing potentially important roles in BCBM in BC patients.", "claims": [{"id": "claim-method", "statement": "The GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r/) based on R language limma package was used to analyze the gene expression data and to identify DEGs [24].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34541602", "locator": "sections[4] \"Data processing\" paragraph 2", "quote": "The GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r/) based on R language limma package was used to analyze the gene expression data and to identify DEGs [24]."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "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:34541602"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34541602", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1042/BSR20211615", "sha256": 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"PMC8521534", "section_index": 13, "section_title": "KEGG pathway and GO term enrichment analyses", "row_count": 30, "column_count": 4}, "table": {"label": "Table 1", "caption": "GO functional enrichment analysis for the DEGs", "rows": [["Term", "Category", "P-value", "UniProt ID"], ["BP"], ["Extracellular matrix organization", "GO:0030198", "2.66E-15", "COL1A1, COL3A1, COL14A1, LAMA4, COL6A2, COL5A3, COL5A2, COL6A1, COL6A3"], ["Collagen fibril organization", "GO:0030199", "3.10E-09", "COL1A1, COL3A1, COL14A1, COL5A3, COL5A2"], ["Cellular response to amino acid stimulus", "GO:0071230", "1.71E-06", "COL1A1, COL3A1, COL5A2, COL6A1"], ["Cell adhesion", "GO:0007155", "1.72E-06", "COL1A1, COL15A1, LAMA4, COL6A2, COL6A1, COL6A3"], ["Protein heterotrimerization", "GO:0070208", "2.32E-05", "COL1A1, COL6A2, COL6A1"], ["Skin development", "GO:0043588", "1.42E-04", "COL3A1, COL5A3, COL5A2"], ["Skeletal system development", "GO:0001501", "0.00229126", "COL1A1, COL3A1, COL5A2"], ["Blood vessel development", "GO:0001568", "0.020188218", "COL1A1, LAMA4"], ["Cell–matrix adhesion", "GO:0007160", "0.047226948", "COL3A1, COL5A3"], ["Osteoblast differentiation", "GO:0001649", "0.054392332", "COL1A1, COL6A1"], ["Platelet activation", "GO:0030168", "0.059988631", "COL1A1, COL3A1"], ["Regulation of immune response", "GO:0050776", "0.091476749", "COL1A1, COL3A1"], ["MF"], ["Extracellular matrix structural constituent", "GO:0005201", "2.59E-13", "COL1A1, COL3A1, COL15A1, COL14A1, LAMA4, COL5A3, COL5A2"], ["Platelet-derived growth factor binding", "GO:0048407", "1.39E-05", "COL1A1, COL3A1, COL6A1"], ["SMAD binding", "GO:0046332", "0.022698305", "COL3A1, COL5A2"], ["Collagen binding", "GO:0005518", "0.03154496", "COL14A1, COL5A3"], ["CC"], ["Endoplasmic reticulum lumen", "GO:0005788", "2.66E-15", "COL1A1, COL3A1, COL15A1, COL6A2, COL5A3, COL5A2, COL6A1, COL6A3"], ["Collagen trimer", "GO:0005581", "3.10E-09", "COL1A1, COL3A1, COL14A1, LAMA4, COL6A2, COL5A3, COL5A2, COL6A1, COL6A3"], ["Extracellular matrix", "GO:0031012", "1.71E-06", "COL1A1, COL3A1, COL14A1, COL5A3, COL5A2"], ["Extracellular region", "GO:0005576", "1.72E-06", "COL1A1, COL3A1, COL5A2, COL6A1"], ["Proteinaceous extracellular matrix", "GO:0005578", "2.32E-05", "COL1A1, COL15A1, LAMA4, COL6A2, COL6A1, COL6A3"], ["Extracellular space", "GO:0005615", "1.42E-04", "COL1A1, COL6A2, COL6A1"], ["Extracellular exosome", "GO:0070062", "0.00229126", "COL3A1, COL5A3, COL5A2"], ["Sarcolemma", "GO:0042383", "0.020188218", "COL1A1, COL3A1, COL5A2"], ["Collagen type V trimer", "GO:0005588", "0.047226948", "COL1A1, LAMA4"], ["Collagen type VI trimer", "GO:0005589", "2.98E-16", "COL3A1, COL5A3"]], "row_count": 30, "column_count": 4, "numeric_cells": 61, "header_rows": 1, "locator": "section[13]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:34541602:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ba3529fdb262907f5b3a7bd9c95a8118d286fc28da4f6d484217cdfd2662ab19", "bytes": 860, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[2]#T2", "version": null, "note": "Pathway enrichment analysis for the DEGs", "structure": {"pmcid": "PMC8521534", "section_index": 13, "section_title": "KEGG pathway and GO term enrichment analyses", "row_count": 7, "column_count": 4}, "table": {"label": "Table 2", "caption": "Pathway enrichment analysis for the DEGs", "rows": [["Term", "Category", "P-value", "UniProt ID"], ["Protein digestion and absorption", "hsa04974", "4.62E-15", "COL1A1, COL3A1, COL15A1, COL14A1, COL6A2, COL5A3, COL5A2, COL6A1, COL6A3"], ["ECM–receptor interaction", "hsa04512", "1.43E-12", "COL1A1, COL3A1, LAMA4, COL6A2, COL5A3, COL5A2, COL6A1, COL6A3"], ["Focal adhesion", "hsa04510", "6.68E-10", "COL1A1, COL3A1, LAMA4, COL6A2, COL5A3, COL5A2, COL6A1, COL6A3"], ["PI3K-Akt signaling pathway", "hsa04151", "2.48E-08", "COL1A1, COL3A1, LAMA4, COL6A2, COL5A3, COL5A2, COL6A1, COL6A3"], ["Amoebiasis", "hsa05146", "6.33E-06", "COL1A1, COL3A1, LAMA4, COL5A3, COL5A2"], ["Platelet activation", "hsa04611", "5.10E-04", "COL1A1, COL3A1, COL5A3, COL5A2"]], "row_count": 7, "column_count": 4, "numeric_cells": 13, "header_rows": 1, "locator": "section[13]/table-wrap[2]#T2"}}, {"id": "asset:table:pmid:34541602:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:2ff0aadb5b86a71ae1dd2e3fc57db429a19e7b1f7d7611d382e75d046c973a5c", "bytes": 710, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#T3", "version": null, "note": "The potential TFs of ten hub genes", "structure": {"pmcid": "PMC8521534", "section_index": 15, "section_title": "TF regulatory network analysis of ten genes", "row_count": 11, "column_count": 3}, "table": {"label": "Table 3", "caption": "The potential TFs of ten hub genes", "rows": [["Genes", "TFs", "Counts"], ["LAMA4", "ATF71IP, BRD7, USF2, CREB1, GATA1, TP53, GATA2, GATA3, MED31, ZHX1, EEF1A1", "11"], ["COL1A1", "SP3, JUN, MYB, NFKB1, POU2F1, RELA, SP1FLI1, EGR1, SMAD1, WFIC", "10"], ["COL5A2", "MEF2A, FOXO3B, TBP, PBX1, FOXO1, FOXO4, FOXO3, REL", "8"], ["COL3A1", "SMAD1, IRF1, NFIC, SMAD3, JUN", "5"], ["COL4A1", "STAT2, ZEB1, CTCF, STAT1", "4"], ["COL5A1", "IILF, REL, PPARG, ATF2", "4"], ["COL5A3", "REST, RREB1, MEIS1, TFAP4", "4"], ["COL6A3", "ZBTB6, SMAD3, WFIC", "3"], ["COL6A2", "NFIC, TFAP2A", "2"], ["COL6A1", "SMAD3", "1"]], "row_count": 11, "column_count": 3, "numeric_cells": 11, "header_rows": 1, "locator": "section[15]/table-wrap[1]#T3"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", 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