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pmid:28472085
Transcriptomic immunologic signature associated with favorable clinical outcome in basal-like breast tumors.
Sandra Martínez-Canales · Francisco Cifuentes · Miguel López De Rodas Gregorio · Leticia Serrano-Oviedo · Eva María Galán-Moya · Eitan Amir · Atanasio Pandiella · Balázs Győrffy · Alberto Ocaña
PloS one · 2017 doi:10.1371/journal.pone.0175128
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Activation of the immune system is associated with tumor response and may help identify TNBC with favorable outcome.\nMETHODS: Gene expression data were obtained from the GEO Dataset GDS2250/GSE3744. Affymetrix CEL files were downloaded and analyzed with Affymetrix Transcriptome Analysis Console 3.0. Functional genomics was implemented with David Bioinformatics Resources 6.8. Data contained at Oncomine were used to identify genes upregulated in basal-like cancer compared to normal breast tissue. Data contained at cBioportal were used to assess for molecular alterations. The KMPlotter online tool, METABRIC and GSE25066 datasets were used to associate gene signatures with clinical outcome.\nRESULTS: 1564 upregulated genes were identified as differentially expressed between normal and basal-like tumors. Of these, 16 genes associated with immune function were linked with clinical outcome. HLA-C, HLA-F, HLA-G and TIGIT were associated with both improved relapse-free survival (RFS) and overall survival (OS). The combination of HLA-F/TIGIT and HLA-C/HLA-F/TIGIT showed the most favorable outcome (HR for RFS 0.44, p<0.001; HR for OS 0.22, p<0.001; and HR for RFS 0.46, p<0.001; HR for OS 0.15, p<0.001; respectively). The association of HLA-C/HLA-F with outcome was confirmed using the METABRIC and GSE25066 datasets. No copy number alterations of these genes were identified.\nCONCLUSION: We describe a gene signature associated with immune function and favorable outcome in basal-like breast cancer. Incorporation of this signature in prospective studies may help to stratify risk of early stage TNBC.", "claims": [{"id": "claim-method", "statement": "The KM Plotter Online Tool was used to analyze the relationship between the gene expression and patient clinical outcome in breast cancer (http://www.kmplot.com); this public database allowed us to investigate overall survival (OS) and relapse-free survival (RFS) [11].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28472085", "locator": "sections[4] \"Outcome analyses\" paragraph 2", "quote": "The KM Plotter Online Tool was used to analyze the relationship between the gene expression and patient clinical outcome in breast cancer (http://www.kmplot.com); this public database allowed us to investigate overall survival (OS) and relapse-free survival (RFS) [11]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All relevant data are within the paper and its Supporting Information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28472085", "locator": "sections[13] \"Data Availability\" paragraph 2", "quote": "All relevant data are within the paper and its Supporting Information files."}], "state": "complete"}, {"id": "claim-target-result", "statement": "An in silico survival analysis using KM Plotter, with confirmation in the METABRIC and GSE25066 datasets, found that HLA-F/TIGIT and HLA-C/HLA-F/TIGIT signatures were associated with the most favorable relapse-free and overall survival in basal-like breast cancer.", "kind": "quantitative", "target": {"value": 0.001, "unit": "p-value", "tolerance": null, "source": "The combination of HLA-F/TIGIT and HLA-C/HLA-F/TIGIT showed the most favorable outcome (HR for RFS 0.44, p<0.001; HR for OS 0.22, p<0.001; and HR for RFS 0.46, p<0.001; HR for OS 0.15, p<0.001; respectively)."}, "evidence": [{"asset": "source:pmid:28472085", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The combination of HLA-F/TIGIT and HLA-C/HLA-F/TIGIT showed the most favorable outcome (HR for RFS 0.44, p<0.001; HR for OS 0.22, p<0.001; and HR for RFS 0.46, p<0.001; HR for OS 0.15, p<0.001; respectively)."}, {"asset": "source:pmid:28472085", "locator": "sections[4] \"Outcome analyses\" paragraph 2", "quote": "The KM Plotter Online Tool was used to analyze the relationship between the gene expression and patient clinical outcome in breast cancer (http://www.kmplot.com); this public database allowed us to investigate overall survival (OS) and relapse-free survival (RFS) [11]."}, {"asset": "source:pmid:28472085", "locator": "sections[4] \"Outcome analyses\" paragraph 3", "quote": "We also confirmed the results using two additional datasets: METABRIC [13] and the GSE25066 dataset [14]."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "An in silico survival analysis using KM Plotter, with confirmation in the METABRIC and GSE25066 datasets, found that HLA-F/TIGIT and HLA-C/HLA-F/TIGIT signatures were associated with the most favorable relapse-free and overall survival in basal-like breast cancer.", "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:28472085"], "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. 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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": "asset:table:pmid:28472085:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:122186a3fd48df697b7ded141f7522ff8cc642bcb4a356fae01343bcd963f051", "bytes": 1579, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[1]#pone.0175128.t001", "version": null, "note": "List of the identified immunologic-related genes associated with RFS and OS in basal like breast cancer.", "structure": {"pmcid": "PMC5417488", "section_index": 9, "section_title": "Gene set combinations for HLA-C, HLA-F, HLA-G and TIGIT", "row_count": 13, "column_count": 6}, "table": {"label": "Table 1", "caption": "List of the identified immunologic-related genes associated with RFS and OS in basal like breast cancer.", "rows": [["Probe Set", "Gene name", "Basal Like"], ["Relapse Free Survival", "Overall Survival"], ["HR (Hazard Ratio)", "Logrank P-value", "HR (Hazard Ratio)", "Logrank P-value"], ["217072_at", "CD300A, CD300a molecule", "0,74 (0,57–0,96)", "0,023", "-", ">0,05"], ["211893_x_at", "CD6, CD6 molecule", "0,53 (0,4–0,69)", "2,20E-06", "-", ">0,05"], ["222859_s_at", "DAPP1, dual adaptor of phosphotyrosine and 3-phosphoinositides", "0,5 (0,35–0,7)", "5,50E-05", "-", ">0,05"], ["211799_x_at", "HLA-C, major histocompatibility complex, class I, C", "0,59 (0,45–0,77)", "9,90E-05", "0,38 (0,21–0,71)", "0,0014"], ["221875_x_at", "HLA-F, major histocompatibility complex, class I, F", "0,53 (0,41–0,7)", "2,80E-06", "0,35 (0,19–0,63)", "0,00032"], ["211528_x_at", "HLA-G, major histocompatibility complex, class I, G", "0,6 (0,46–0,79)", "0,00017", "0,42 (0,23–0,75)", "0,0028"], ["239021_at", "TLR6, toll-like receptor 6", "0,67 (0,48–0,95)", "0,023", "-", ">0,05"], ["210340_s_at", "CSF2RA, colony stimulating factor 2 receptor, alpha, low-affinity (granulocyte-macrophage)", "0,59 (0,45–0,76)", "6,80E-05", "-", ">0,05"], ["240070_at", "TIGIT, T cell immunoreceptor with Ig and ITIM domains", "0,36 (0,25–0,52)", "8,30E-09", "0,37 (0,16–0,84)", "0,014"], ["1564684_at", "BTN2A2, butyrophilin, subfamily 2, member A2", "0,55 (0,39–0,78)", "0,00072", "-", ">0,05"]], "row_count": 13, "column_count": 6, "numeric_cells": 49, "header_rows": 3, "locator": "section[9]/table-wrap[1]#pone.0175128.t001"}}, {"id": "asset:table:pmid:28472085:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:77a35e8106c7274ef356a8edc08c64b5058b739cedbb9607c755f369bcfc6911", "bytes": 1516, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[2]#pone.0175128.t002", "version": null, "note": "List of gene combinations associated with favorable outcome in basal like cancer using the KM plotter online tool, as described in material and methods.", "structure": {"pmcid": "PMC5417488", "section_index": 9, "section_title": "Gene set combinations for HLA-C, HLA-F, HLA-G and TIGIT", "row_count": 13, "column_count": 7}, "table": {"label": "Table 2", "caption": "List of gene combinations associated with favorable outcome in basal like cancer using the KM plotter online tool, as described in material and methods.", "rows": [["Gene combinations", "Relapse Free Survival", "Overall Survival"], ["HR (Hazard Ratio)", "Logrank P- value", "N (patients)", "HR (Hazard Ratio)", "Logrank P- value", "N (patients)"], ["HLA-C, HLA-F, HLA-G, TIGIT", "0,54 (0,38–0,77)", "0.00047", "339", "0,2 (0,08–0,54)", "0,00036", "132"], ["HLA-C, HLA-F, HLA-G", "0,55 (0,42–0,72)", "7,8E-06", "580", "0,38 (0,21–0,7)", "0,0011", "204"], ["HLA-C, HLA-F, TIGIT", "0,46 (0,32–0,65)", "7,5E-06", "339", "0,15 (0,05–0,44)", "6,2E-05", "132"], ["HLA-C, HLA-G, TIGIT", "0,56 (0,4–0,79)", "0,00081", "339", "0,15 (0,05–0,44)", "6,7E-05", "132"], ["HLA-F, HLA-G, TIGIT", "0,5 (0,35–0,71)", "7,8E-05", "339", "0,25 (0,1–0,62)", "0,0012", "132"], ["HLA-C, HLA-F", "0,51 (0,39–0,67)", "6,2E-07", "580", "0,31 (0,16–0,58)", "0,00011", "204"], ["HLA-C, HLA-G", "0,62 (0,47–0,8)", "0,00029", "580", "0,39 (0,21–0,71)", "0,0014", "204"], ["HLA-C, TIGIT", "0,58 (0,41–0,81)", "0,0015", "339", "0,21 (0,08–0,57)", "0,00063", "132"], ["HLA-F, HLA-G", "0,57 (0,44–0,75)", "3,5E-05", "580", "0,42 (0,23–0,76)", "0,0029", "204"], ["HLA-F, TIGIT", "0,44 (0,31–0,63)", "3E-06", "339", "0,22 (0,09–0,55)", "0,00037", "132"], ["HLA-G, TIGIT", "0,57 (0,4–0,81)", "0,0013", "339", "0,19 (0,07–0,51)", "2E-04", "132"]], "row_count": 13, "column_count": 7, "numeric_cells": 66, "header_rows": 2, "locator": "section[9]/table-wrap[2]#pone.0175128.t002"}}], "gaps": ["asset:data:geo:GSE25066 not downloaded", "asset:data:geo:GSE25066 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