Clinicopathological Significances of Cancer Stem Cell-Associated HHEX Expression in Breast Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33425911", "kind": "science-record", "revision": 7, "content_hash": "sha256:a09eccae7dd11a050afdd298ffb90738edf3f4a5b31420fea8d9300b66a9cec0", "created_at": "2026-11-01T15:41:22Z", "updated_at": "2026-11-01T22:02:55Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Clinicopathological Significances of Cancer Stem Cell-Associated HHEX Expression in Breast Cancer.", "doi": "10.3389/fcell.2020.605744", "pmid": "33425911", "authors": ["Kexin Zhang", "Qi Zhao", "Zugui Li", "Fangmei Fu", "Hao Zhang", "Junjie Fu", "Minying Zheng", "Shiwu Zhang"], "journal": "Frontiers in cell and developmental biology", "year": 2020, "abstract": "Aberrant expression of the transcription factor hematopoietic ally expressed homeobox/proline-rich homeodomain (HHEX/PRH) is implicated in numerous cancers. However, the association of HHEX with breast cancer (BC) remains unclear. In this study, HHEX mRNA and protein expression were analyzed using the Oncomine, UALCAN, GEPIA, TCGAportal, and HPA databases. We evaluated the effect of HHEX on clinicopathological parameters using Kaplan-Meier plotter, OncoLnc, TCGAportal, PROGgeneV2, and BC-GenExMiner. Western blotting was performed to compare the level of HHEX in breast samples of Tientsin Albino 2 mice, human breast precancerous lesions, benign breast tumors, and BC. The correlation between HHEX and cancer stem cells was investigated using the GEO (GSE52327 and GSE94865) and GEPIA datasets. Networks between HHEX and survival-related gene marker sets and microRNAs were analyzed using GEPIA, StarBase, and Cytoscape. Results of this study showed that HHEX expression in BC was significantly lower than those in breast precancerous lesions and benign breast tumors at both mRNA and protein levels. BC patients with lower HHEX expression had significantly worse overall survival and disease-free survival. Moreover, HHEX significantly affected the clinicopathology of BC. Specifically, low HHEX expression was correlated with the following groups of patients: age ≤51 years, ER-negative or PR-negative patients, HER-2 positive, triple-negative breast cancer, and basal-like BC. Immunohistochemical analysis of the breast samples showed significant differences of HHEX staining index (P < 0.001) among the three groups. To further investigate the mechanism, we determined the intersection of differentially expressed genes related to BC stem cells and those genes after HHEX expression was altered. This led to the identification of four potentially regulated genes-CXL12, BLNK, PAG1, and LPXN. Using StarBase and km-plotter, the negative regulation of HHEX expression and survival trends, including miR-130b, miR-30e, and miR-301b were joined into miRNA-HHEX-mRNA potential regulatory network. The abilities of proliferation, migration and invasion increased in MDA-MB-231 and BT-549 breast cancer cell lines after HHEX down expression and decreased after HHEX overexpression compared them in the control cells. In conclusion, these data suggest that HHEX expression is downregulated in BC and HHEX may regulate the development of BC through the stem cell-related genes.", "claims": [{"id": "claim-method", "statement": "The Wilcoxon rank sum test was used to assess the significance of the observed differences.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33425911", "locator": "sections[3] \"HHEX Expression Level Analysis\" paragraph 2", "quote": "The Wilcoxon rank sum test was used to assess the significance of the observed differences."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Materials, further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33425911", "locator": "sections[33] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Materials, further inquiries can be directed to the corresponding author."}], "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:33425911"], "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:GSE52327"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "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:GSE52327"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33425911", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcell.2020.605744", "sha256": "sha256:d2a3dcb9c171d83296fccc83138bf8bf87fd842a911d140a103902ae0660f174", "bytes": 58354, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcell.2020.605744", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7785851", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE52327", "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=GSE52327", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE52327", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Materials, further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Materials, further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1263184", "GSM1263185", "GSM1263186", "GSM1263187", "GSM1263188", "GSM1263189", "GSM1263190", "GSM1263191", "GSM1263192", "GSM1263193", "GSM1263194", "GSM1263195", "GSM1263196", "GSM1263197", "GSM1263198", "GSM1263199"], "sample_count": 16, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Expression data of ALDH+ breast cancer cells", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE94865", "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=GSE94865", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE94865", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Materials, further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Materials, further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2486657", "GSM2486658", "GSM2486659", "GSM2486660", "GSM2486661", "GSM2486662", "GSM2486663", "GSM2486664", "GSM2486665", "GSM2486666", "GSM2486667", "GSM2486668"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "18943", "taxon": "Homo sapiens", "title": "Gene expression changes following knockdown or overexpression of HHEX/PRH", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33425911:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:41f8f2a261585ac56eaa925bad997cba9273415694c72adf287fad5709682036", "bytes": 2450, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[1]#T1", "version": null, "note": "Summary of databases used in this study.", "structure": {"pmcid": "PMC7785851", "section_index": 18, "section_title": "HHEX Expression Levels in Pan-Cancer and BC Patients", "row_count": 14, "column_count": 4}, "table": {"label": "Table 1", "caption": "Summary of databases used in this study.", "rows": [["Name", "Link", "This study", "Keywords"], ["Oncomine", "https://www.oncomine.org/resource/main.html", "To analyze the HHEX mRNA expression in different cancers", "Gene expression"], ["UALCAN", "http://ualcan.path.uab.edu/", "To analyze the HHEX mRNA expression in different molecular subtypes of BC patients", "Gene expression; 16 cancer types; survival curve; DNA methylation"], ["GEPIA", "http://gepia.cancer-pku.cn/detail.php", "To assess the correlations between genes", "Gene expression; survival curve; isoform details; genes correlation; similar genes detection"], ["TCGAportal", "http://www.tcgaportal.org", "To investigate the expression and survival of HHEX in human tissues", "Gene expression; 28 cancer types; survival curve; DNA methylation; mutation"], ["Human Protein Atlas", "https://www.proteinatlas.org/", "To detect HHEX protein expression and survival", "Proteins distribution; subcellular localization; impact for survival"], ["Kaplan-Meier Plotter", "http://kmplot.com/analysis/index.php?p=background", "To analyzed the correlations between genes and miRNAs expression and RFS as well as OS", "Breast cancer; subtype; survival curve"], ["OncoLnc", "https://www.oncolnc.org/", "To detect HHEX survival", "Breast cancer; survival curve"], ["PROGgeneV2", "http://genomics.jefferson.edu/proggene/", "", "Gene expression; breast cancer; subtype; survival curve"], ["bc-GenExMiner", "http://bcgenex.centregauducheau.fr/BC-GEM/GEM-Accueil.php?js=1", "To compute breast cancer gene-expression correlation analyses, for gene prognostic analyses", "Gene-expression correlation; gene prognostic analyses"], ["cBioportal", "http://www.cbioportal.org/", "To detect HHEX genetic alterations", "Genetic alterations; survival curve"], ["GEO", "https://www.ncbi.nlm.nih.gov/geo/", "To selected data sets related to breast cancer stem cells to explore further mechanisms", "Gene expression; datasets details"], ["STRING", "https://string-db.org/cgi/input.pl", "To obtain the interaction network between HHEX and other important proteins", "Protein details; interactive network; functional enrichment"], ["starBase v3.0", "http://starbase.sysu.edu.cn/index.php", "To predict the miRNAs related to HHEX; To perform miRNAs as well as correlation analysis between miRNAs and HHEX mRNA", "miRNA target; Pan-cancer"]], "row_count": 14, "column_count": 4, "numeric_cells": 4, "header_rows": 1, "locator": "section[18]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:33425911:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:a6d08e87433f76f4f86ae803e75e11f273a8b431eb9e5205bcfcf80f9a55d52a", "bytes": 524, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[20]/table-wrap[1]#T2A", "version": null, "note": "The differences of HHEX staining index among 53 cases of precancerous lesions (group I), 44 cases of primary BC (group II), and 48 cases of benign breast tumors (group III).", "structure": {"pmcid": "PMC7785851", "section_index": 20, "section_title": "HHEX Expression in Human BC Tissues", "row_count": 4, "column_count": 5}, "table": {"label": "Table 2A", "caption": "The differences of HHEX staining index among 53 cases of precancerous lesions (group I), 44 cases of primary BC (group II), and 48 cases of benign breast tumors (group III).", "rows": [["Group", "n", "Staining index for HHEX", "Value of statistic", "P"], ["Group I", "53", "4.19 ± 2.067", "χ2 = 25.081", "0.001"], ["Group II", "44", "2.11 ± 1.224", "", ""], ["Group III", "48", "4.77 ± 2.363", "", ""]], "row_count": 4, "column_count": 5, "numeric_cells": 8, "header_rows": 1, "locator": "section[20]/table-wrap[1]#T2A"}}, {"id": "asset:table:pmid:33425911:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:9384295e149ef99d010a6a3188abb58902d964ad6e967104a357078fdaef9247", "bytes": 422, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[20]/table-wrap[2]#T2B", "version": null, "note": "The difference of HHEX staining index between among 53 cases of precancerous lesions (group I) and 44 cases of primary BC (group II).", "structure": {"pmcid": "PMC7785851", "section_index": 20, "section_title": "HHEX Expression in Human BC Tissues", "row_count": 3, "column_count": 5}, "table": {"label": "Table 2B", "caption": "The difference of HHEX staining index between among 53 cases of precancerous lesions (group I) and 44 cases of primary BC (group II).", "rows": [["Group", "N", "Staining index for HHEX", "Z", "P"], ["Group I", "53", "4.19 ± 2.067", "−4.139", "0.001"], ["Group II", "44", "2.11 ± 1.224", "", ""]], "row_count": 3, "column_count": 5, "numeric_cells": 6, "header_rows": 1, "locator": "section[20]/table-wrap[2]#T2B"}}, {"id": "asset:table:pmid:33425911:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c311282de6e329652655096bcc7b86f164a4a1758e858afda42fe0b23cd53830", "bytes": 420, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[20]/table-wrap[3]#T2C", "version": null, "note": "The difference of HHEX staining index between 44 cases of primary BC (group II) and 48 cases of benign breast tumors (group III).", "structure": {"pmcid": "PMC7785851", "section_index": 20, "section_title": "HHEX Expression in Human BC Tissues", "row_count": 3, "column_count": 5}, "table": {"label": "Table 2C", "caption": "The difference of HHEX staining index between 44 cases of primary BC (group II) and 48 cases of benign breast tumors (group III).", "rows": [["Group", "n", "Staining index for HHEX", "Z", "P"], ["Group II", "44", "2.11 ± 1.224", "−4.641", "0.001"], ["Group III", "48", "4.77 ± 2.363", "", ""]], "row_count": 3, "column_count": 5, "numeric_cells": 6, "header_rows": 1, "locator": "section[20]/table-wrap[3]#T2C"}}, {"id": "asset:table:pmid:33425911:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:343abacc14a657884c47e94e9bbacbae7265b5709c97c17aa4e06ebd36b87690", "bytes": 1424, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[22]/table-wrap[1]#T3", "version": null, "note": "Correlation between HHEX expression and clinicopathological features.", "structure": {"pmcid": "PMC7785851", "section_index": 22, "section_title": "Relationship Between HHEX and Clinicopathological Parameters of BC Patients", "row_count": 21, "column_count": 5}, "table": {"label": "Table 3", "caption": "Correlation between HHEX expression and clinicopathological features.", "rows": [["", "OS", "RFS"], ["Characteristic", "HR (95% CI)", "Log rank P", "HR (95% CI)", "Log rank P"], ["GENE SYMBOL: HHEX, affy id:215933_s_at"], ["ER status", "", "", "", ""], ["ER positive", "0.88(0.62–1.26)", "0.4927", "0.82(0.7–0.97)", "0.0191"], ["ER negative", "0.78(0.49–1.23)", "0.2826", "0.82(0.65–1.02)", "0.0792"], ["HER2 status", "", "", "", ""], ["HER2 positive", "1.52(0.74–3.12)", "0.2518", "0.83(0.54–1.28)", "0.3982"], ["HER2 negative", "1.06(0.45–2.51)", "0.8886", "0.68(0.52–0.88)", "0.0038"], ["Lymph node status", "", "", "", ""], ["Lymph node positive", "0.65(0.44–0.96)", "0.0278", "0.63(0.52–0.77)", "4.00E-06"], ["Lymph node negative", "0.92(0.63–1.33)", "0.6414", "0.75(0.63–0.89)", "0.0009"], ["Grade", "", "", "", ""], ["1", "1.25(0.52–3.02)", "0.6169", "0.86(0.51–1.45)", "0.5758"], ["2", "0.78(0.5–1.2)", "0.2502", "0.73(0.57–0.93)", "0.0094"], ["3", "0.85(0.61–1.18)", "0.3365", "0.9(0.72–1.12)", "0.3396"], ["Intrinsic subtype", "", "", "", ""], ["Basal", "0.8(0.49–1.3)", "0.3599", "0.64(0.5–0.83)", "0.0006"], ["luminal A", "0.72(0.5–1.02)", "0.066", "0.74(0.62–0.88)", "0.0006"], ["luminal B", "0.94(0.65–1.36)", "0.7459", "0.69(0.57–0.84)", "2.00E-04"], ["HER2+", "0.29(0.14–0.6)", "0.0004", "0.56(0.38–0.83)", "0.0033"]], "row_count": 21, "column_count": 5, "numeric_cells": 58, "header_rows": 2, "locator": "section[22]/table-wrap[1]#T3"}}], "gaps": ["asset:data:geo:GSE52327 not downloaded", "asset:data:geo:GSE52327 licence not read", "asset:data:geo:GSE94865 not downloaded", "asset:data:geo:GSE94865 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The Wilcoxon rank sum test was used to assess the significance of the observed differences."}}, {"id": "method-2", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Student's t-test"}}, {"id": "method-3", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "ANOVA"}}, {"id": "method-4", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "Kaplan-Meier"}}, {"id": "method-5", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log rank"}}, {"id": "method-6", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "PPI"}}, {"id": "method-7", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "pathway enrichment"}}], "targets": [], "gaps": ["method.group_comparison_wilcoxon"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE52327", "GSE94865"], "resolved_accessions": ["GSE52327", "GSE94865"], "statements": ["The original contributions presented in the study are included in the article/Supplementary Materials, further inquiries can be directed to the corresponding author."], "basis": "The paper names GSE52327, GSE94865 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:33425911", "data:geo:GSE52327", "asset:table:pmid:33425911:1", "asset:table:pmid:33425911:2", "asset:table:pmid:33425911:3", "asset:table:pmid:33425911:4", "asset:table:pmid:33425911:5"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_wilcoxon", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE52327"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:26:06Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 48245, "completion_tokens": 1934, "cached_tokens": 784}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:33425911", "type": "paper", "label": "pmid:33425911"}, {"id": "source:pmid:33425911", "type": "manuscript", "label": "PMID 33425911 full text"}, {"id": "data:geo:GSE52327", "type": "dataset", "label": "GEO GSE52327"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33425911", "type": "paper", "label": "pmid:33425911"}, {"id": "source:pmid:33425911", "type": "manuscript", "label": "PMID 33425911 full text"}, {"id": "data:geo:GSE52327", "type": "dataset", "label": "GEO GSE52327"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33425911", "type": "extraction", "used": ["source:pmid:33425911"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE52327", "type": "accession_resolution", "used": ["data:geo:GSE52327"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:33425911", "parent_hash": "sha256:c1aba7d6d3ebad7de8ca1f56274b05db6675b0da234882217854ace8f0912c03", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE52327 licence not read", "asset:data:geo:GSE52327 not downloaded", "asset:data:geo:GSE94865 licence not read", "asset:data:geo:GSE94865 not downloaded", "execution.not_run", "method.group_comparison_wilcoxon", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:group_comparison_wilcoxon"], "assays": [{"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": [", TCGAportal, PROGgeneV2, and BC-GenExMiner. Western blotting was performed to compare the level of HHEX i", "ls of HHEX. (a) Expression levels of HHEX by western blot analysis in TA2 mice with different numbers"], "order_basis": "paper_text_order:559", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["e-negative breast cancer, and basal-like BC. Immunohistochemical analysis of the breast samples showed signif", "HHEX protein expression in BC, we found that immunohistochemical analysis of HHEX was negative in BC and norm", "ifferent numbers of pregnancies and SBC. (C) Immunohistochemical (IHC) staining of HHEX expression in human b", "regnancies and SBC. (C) Immunohistochemical (IHC) staining of HHEX expression in human breast"], "order_basis": "paper_text_order:1540", "id": "assay:2"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The Wilcoxon rank sum test was used to assess the significance of the observed differences."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}