The role of AKR1 family in tamoxifen resistant invasive lobular breast cancer based on data mining.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34886806", "kind": "science-record", "revision": 5, "content_hash": "sha256:9d548fd7bd50938423061746415b9bec73d05463e2f313b35b099a1fd74e6448", "created_at": "2026-11-01T17:36:35Z", "updated_at": "2026-11-01T22:48:01Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The role of AKR1 family in tamoxifen resistant invasive lobular breast cancer based on data mining.", "doi": "10.1186/s12885-021-09040-8", "pmid": "34886806", "authors": ["Dong Xu", "Yiqi Zhang", "Feng Jin"], "journal": "BMC cancer", "year": 2021, "abstract": "BACKGROUND: Tamoxifen (TAM) resistance to invasive lobular cell carcinoma is a challenge for breast cancer treatment. This study explored the role of Aldo-keto reductase family 1 (AKR1) family in tamoxifen-resistant aggressive lobular breast cancer based on data mining.\nMETHODS: TAM-resistant invasive lobular breast cancer gene chip was downloaded from the Gene Expression Omnibus (GEO) database (accession-numbered as GSE96670). The online analytical tool GEO2R was used to screen for differentially expressed genes in TAM-resistant invasive lobular breast cancer cells and TAM-sensitive counterparts. A protein-protein interaction (PPI) networks were constructed using the STRING online platform and the Cytoscape software. GeneMANIA and GSCALite online tools were used to reveal the potential role of these hub genes in breast cancer progression and TAM resistance development. And the used the GSE67916 microarray data set to verify the differentially expression of these hub genes in breast cancer. The protein expression levels of AKR1C1, AKR1C2 and AKR1C3 in TAM-sensitive and resistant breast cancer cells were compared. The TAM sensitivity of breast cancer cells with or without AKR1C1, AKR1C2 or AKR1C3 gene manipulation was evaluated by cell viability assay.\nRESULTS: A total of 184 differentially expressed genes were screened. Compared with TAM sensitive breast cancer cells, 162 were up-regulated and 22 were down-regulated. The study identified several hub genes in the PPI network that may be involved in the development of TAM resistance of breast cancer, including signal transducer and activator of transcription 1 (STAT1), estrogen receptor alpha (ESR1), fibronectin1 (FN1), cytochrome P4501B1 (CYP1B1), AKR1C1, AKR1C2, AKR1C3 and uridine diphosphate glucuronosyltransferase (UGT) 1A family genes (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10). Compared with TAM-sensitive counterparts, the expression levels of AKR1C1, AKR1C2, and AKR1C3 were up-regulated in TAM-resistant breast cancer cells.\nCONCLUSIONS: Overexpression of each of these three genes significantly increased the resistance of breast cancer cells to TAM treatment, while their knockdown showed opposite effects, indicating that they are potential therapeutic target for the treatment of TAM-resistant breast cancer.", "claims": [{"id": "claim-method", "statement": "Single-factor analysis of variance was used for the comparison between groups, and SNK-q test was used for further pair-wise comparison.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34886806", "locator": "sections[9] \"Statistical analysis\" paragraph 2", "quote": "Single-factor analysis of variance was used for the comparison between groups, and SNK-q test was used for further pair-wise comparison."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data are available via the corresponding author. The datasets analysed during the current study are available in the Gene Expression Omnibus (GEO) database, numbered GSE96670. (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE96670).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34886806", "locator": "sections[26] \"Availability of data and materials\" paragraph 2", "quote": "All data are available via the corresponding author. The datasets analysed during the current study are available in the Gene Expression Omnibus (GEO) database, numbered GSE96670. (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE96670)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The analysis identified 184 differentially expressed genes, comprising 162 up-regulated and 22 down-regulated genes, and implicated AKR1C1, AKR1C2, and AKR1C3 in tamoxifen resistance.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34886806", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A total of 184 differentially expressed genes were screened. Compared with TAM sensitive breast cancer cells, 162 were up-regulated and 22 were down-regulated."}, {"asset": "source:pmid:34886806", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Compared with TAM-sensitive counterparts, the expression levels of AKR1C1, AKR1C2, and AKR1C3 were up-regulated in TAM-resistant breast cancer cells."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The analysis identified 184 differentially expressed genes, comprising 162 up-regulated and 22 down-regulated genes, and implicated AKR1C1, AKR1C2, and AKR1C3 in tamoxifen resistance.", "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:34886806"], "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:GSE67916"], "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:GSE67916"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34886806", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12885-021-09040-8", "sha256": "sha256:7b44d0a3eb65740a4b45b8fbee4a04abdb35593dc96f13da1a1b9aae8e4c72e7", "bytes": 41733, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12885-021-09040-8", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8662825", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE67916", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE67916", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE67916", "version": null, "note": "All data are available via the corresponding author. The datasets analysed during the current study are available in the Gene Expression Omnibus (GEO) database, numbered GSE96670. (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE96670).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data are available via the corresponding author. The datasets analysed during the current study are available in the Gene Expression Omnibus (GEO) database, numbered GSE96670. 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The datasets analysed during the current study are available in the Gene Expression Omnibus (GEO) database, numbered GSE96670. (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE96670).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data are available via the corresponding author. The datasets analysed during the current study are available in the Gene Expression Omnibus (GEO) database, numbered GSE96670. 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RESULTS: A total of 184 differentially expr", "other pathways, as well as the processes of apoptosis, cell cycle inhibition, epithelial mesenchym"], "order_basis": "paper_text_order:1310", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["t cancer cells to TAM treatment, while their knockdown showed opposite effects, indicating that the", "Co. LTD. The naive cell line (TAM-sensitive) transfected with pcDNA-NC, pcDNA-AKR1C1, pcDNA-AKR1C2 or", "pcDNA-AKR1C3 and the TAM-resistant cell line transfected with pSUPER-si-NC, pSUPER-si-AKR1C1, pSUPER-"], "order_basis": "paper_text_order:2240", "id": "assay:2"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Single-factor analysis of variance was used for the comparison between groups, and SNK-q test was used for further pair-wise comparison."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}