CD133 expression is associated with less DNA repair, better response to chemotherapy and survival in ER-positive/HER2-negative breast cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38585981", "kind": "science-record", "revision": 3, "content_hash": "sha256:9a25e1a4bda6f672f4398c5f704a92431ccbbd0041c2ef4813dd490a4201bcc8", "created_at": "2026-11-01T19:20:33Z", "updated_at": "2026-11-01T22:54:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "CD133 expression is associated with less DNA repair, better response to chemotherapy and survival in ER-positive/HER2-negative breast cancer.", "doi": "10.21203/rs.3.rs-4148608/v1", "pmid": "38585981", "authors": ["Takumi Sato", "Masanori Oshi", "Jing Li Huang", "Kohei Chida", "Arya Mariam Roy", "Itaru Endo", "Kazuaki Takabe"], "journal": "Research square", "year": 2024, "abstract": "Purpose: CD133, a cancer stem cells (CSC) marker, has been reported to be associated with treatment resistance and worse survival in triple-negative breast cancer (BC). However, the clinical relevance of CD133 expression in ER-positive/HER2-negative (ER+/HER2-) BC, the most abundant subtype, remains unknown.\nMethods: The BC cohorts from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1904) and The Cancer Genome Atlas (TCGA, n = 1065) were used to obtain biological variables and gene expression data.\nResults: Epithelial cells were the exclusive source of CD133 gene expression in a bulk BC. CD133-high ER+/HER2- BC was associated with CD24, NOTCH1, DLL1, and ALDH1A1 gene expressions, as well as with WNT/β-Catenin, Hedgehog, and Notchsignaling pathways, all characteristic for CSC. Consistent with a CSC phenotype, CD133-low BC was enriched with gene sets related to cell proliferation, such as G2M Checkpoint, MYC Targets V1, E2F Targets, and Ki67 gene expression. CD133-low BC was also linked with enrichment of genes related to DNA repair, such as BRCA1, E2F1, E2F4, CDK1/2. On the other hand, CD133-high tumors had proinflammatory microenvironment, higher activity of immune cells, and higher expression of genes related to inflammation and immune response. Finally, CD133-high tumors had better pathological complete response after neoadjuvant chemotherapy in GSE25066 cohort and better disease-free survival and overall survival in both TCGA and METABRIC cohorts.\nConclusion: CD133-high ER+/HER2- BC was associated with CSC phenotype such as less cell proliferation and DNA repair, but also with enhanced inflammation, better response to neoadjuvant chemotherapy and better prognosis.", "claims": [{"id": "claim-method", "statement": "Survival analyses were performed using Kaplan-Meier plots with log-rank tests.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38585981", "locator": "sections[6] \"Statistical Analysis\" paragraph 2", "quote": "Survival analyses were performed using Kaplan-Meier plots with log-rank tests."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. TCGA data can be found here: [https://www.cbioportal.org. /Breast Invasive Carcinoma (TCGA, PanCancer Atlas)]. METABRIC data can be found here: [https://www.cbioportal.org. / Breast Cancer (METABRIC, Nature 2012 & Nat Commun 2016)]. Data sets from each of the GEO databases can be downloaded from the following sites and access numbers: [https://www.ncbi.nlm.nih.gov/geo./GSE96058/GSE2034/GSE124647/GSE159956/GSE12276/GSE110590/GSE20194/GSE25066/GSE163882/ GSE20271].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38585981", "locator": "sections[20] \"Data Availability:\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. TCGA data can be found here: [https://www.cbioportal.org. /Breast Invasive Carcinoma (TCGA, PanCancer Atlas)]. METABRIC data can be found here: [https://www.cbioportal.org. / Breast Cancer (METABRIC, Nature 2012 & Nat Commun 2016)]. Data sets from each of the GEO databases can be downloaded from the following sites and access numbers: [https://www.ncbi.nlm.nih.gov/geo./GSE96058/GSE2034/GSE124647/GSE159956/GSE12276/GSE110590/GSE20194/GSE25066/GSE163882/ GSE20271]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "CD133-high ER+/HER2− BC was associated with CSC phenotype such as less cell proliferation and DNA repair, but also with enhanced inflammation, better response to neoadjuvant chemotherapy and better prognosis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38585981", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "CD133-high ER+/HER2− BC was associated with CSC phenotype such as less cell proliferation and DNA repair, but also with enhanced inflammation, better response to neoadjuvant chemotherapy and better prognosis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "CD133-high ER+/HER2− BC was associated with CSC phenotype such as less cell proliferation and DNA repair, but also with enhanced inflammation, better response to neoadjuvant chemotherapy and better prognosis.", "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:38585981"], "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:GSE20194"], "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:GSE20194"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38585981", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21203/rs.3.rs-4148608/v1", "sha256": "sha256:3899be6053bcbb32ad9bb73ae0258ef09d06207b47e676ed8f2da73de7dec97d", "bytes": 48497, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.21203/rs.3.rs-4148608/v1", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10996805", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE20194", "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=GSE20194", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE20194", "version": null, "note": "Publicly available datasets were analyzed in this study. TCGA data can be found here: [https://www.cbioportal.org. /Breast Invasive Carcinoma (TCGA, PanCancer Atlas)]. METABRIC data can be found here: [https://www.cbioportal.org. / Breast Cancer (METABRIC, Nature 2012 & Nat Commun 2016)]. Data sets from each of the GEO databases can be downloaded from the following sites and access numbers: [https://www.ncbi.nlm.nih.gov/geo./GSE96058/GSE2034/GSE124647/GSE159956/GSE12276/GSE110590/GSE20194/GSE25066/GSE163882/ GSE20271].", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. TCGA data can be found here: [https://www.cbioportal.org. /Breast Invasive Carcinoma (TCGA, PanCancer Atlas)]. METABRIC data can be found here: [https://www.cbioportal.org. / Breast Cancer (METABRIC, Nature 2012 & Nat Commun 2016)]. 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TCGA data can be found here: [https://www.cbioportal.org. /Breast Invasive Carcinoma (TCGA, PanCancer Atlas)]. METABRIC data can be found here: [https://www.cbioportal.org. / Breast Cancer (METABRIC, Nature 2012 & Nat Commun 2016)]. Data sets from each of the GEO databases can be downloaded from the following sites and access numbers: [https://www.ncbi.nlm.nih.gov/geo./GSE96058/GSE2034/GSE124647/GSE159956/GSE12276/GSE110590/GSE20194/GSE25066/GSE163882/ GSE20271].", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. TCGA data can be found here: [https://www.cbioportal.org. /Breast Invasive Carcinoma (TCGA, PanCancer Atlas)]. METABRIC data can be found here: [https://www.cbioportal.org. / Breast Cancer (METABRIC, Nature 2012 & Nat Commun 2016)]. Data sets from each of the GEO databases can be downloaded from the following sites and access numbers: [https://www.ncbi.nlm.nih.gov/geo./GSE96058/GSE2034/GSE124647/GSE159956/GSE12276/GSE110590/GSE20194/GSE25066/GSE163882/ GSE20271].", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM615096", "GSM615097", "GSM615098", "GSM615099", "GSM615100", "GSM615101", "GSM615102", "GSM615103", "GSM615104", "GSM615105", "GSM615106", "GSM615107", "GSM615108", "GSM615109", "GSM615110", "GSM615111", "GSM615112", "GSM615113", "GSM615114", "GSM615115", "GSM615116", "GSM615117", "GSM615118", "GSM615119", "GSM615120", "GSM615121", "GSM615122", "GSM615123", "GSM615124", "GSM615125", "GSM615126", "GSM615127", "GSM615128", "GSM615129", "GSM615130", "GSM615131", "GSM615132", "GSM615133", "GSM615134", "GSM615135", "GSM615136", "GSM615137", "GSM615138", "GSM615139", "GSM615140", "GSM615141", "GSM615142", "GSM615143", "GSM615144", "GSM615145", "GSM615146", "GSM615147", 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"platform": "96", "taxon": "Homo sapiens", "title": "Genomic predictor of response and survival following neoadjuvant taxane-anthracycline chemotherapy in breast cancer", "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:GSE32646", "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=GSE32646", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE32646", "version": null, "note": "Publicly available datasets were analyzed in this study. TCGA data can be found here: [https://www.cbioportal.org. /Breast Invasive Carcinoma (TCGA, PanCancer Atlas)]. METABRIC data can be found here: [https://www.cbioportal.org. / Breast Cancer (METABRIC, Nature 2012 & Nat Commun 2016)]. Data sets from each of the GEO databases can be downloaded from the following sites and access numbers: [https://www.ncbi.nlm.nih.gov/geo./GSE96058/GSE2034/GSE124647/GSE159956/GSE12276/GSE110590/GSE20194/GSE25066/GSE163882/ GSE20271].", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. TCGA data can be found here: [https://www.cbioportal.org. /Breast Invasive Carcinoma (TCGA, PanCancer Atlas)]. METABRIC data can be found here: [https://www.cbioportal.org. / Breast Cancer (METABRIC, Nature 2012 & Nat Commun 2016)]. 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