Constitutive gene expression profile segregates toxicity in locally advanced breast cancer patients treated with high-dose hyperfractionated radical radiotherapy.

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The individual sensitivity to x-rays limits the efficiency of the therapy. Prediction of individual sensitivity to radiotherapy could help to select the radiation protocol and to improve treatment results. The aim of this study was to assess the relationship between gene expression profiles of ex vivo un-irradiated and irradiated lymphocytes and the development of toxicity due to high-dose hyperfractionated radiotherapy in patients with locally advanced breast cancer. Raw data from microarray experiments were uploaded to the Gene Expression Omnibus Database http://www.ncbi.nlm.nih.gov/geo/ (GEO accession GSE15341). We obtained a small group of 81 genes significantly regulated by radiotherapy, lumped in 50 relevant pathways. Using ANOVA and t-test statistical tools we found 20 and 26 constitutive genes (0 Gy) that segregate patients with and without acute and late toxicity, respectively. Non-supervised hierarchical clustering was used for the visualization of results. Six and 9 pathways were significantly regulated respectively. Concerning to irradiated lymphocytes (2 Gy), we founded 29 genes that separate patients with acute toxicity and without it. Those genes were gathered in 4 significant pathways. We could not identify a set of genes that segregates patients with and without late toxicity. In conclusion, we have found an association between the constitutive gene expression profile of peripheral blood lymphocytes and the development of acute and late toxicity in consecutive, unselected patients. These observations suggest the possibility of predicting normal tissue response to irradiation in high-dose non-conventional radiation therapy regimens. Prospective studies with higher number of patients are needed to validate these preliminary results.", "claims": [{"id": "claim-method", "statement": "Identification of differentially-expressed genes was performed using the SAM (Significance Analysis for Microarrays) statistical technique [14].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:19497124", "locator": "sections[2] \"Patients and methods\" paragraph 2", "quote": "Identification of differentially-expressed genes was performed using the SAM (Significance Analysis for Microarrays) statistical technique [14]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Raw data from microarray experiments were uploaded to the Gene Expression Omnibus Database (GEO accession GSE15341).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:19497124", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Raw data from microarray experiments were uploaded to the Gene Expression Omnibus Database (GEO accession GSE15341)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper found that constitutive gene-expression profiles in un-irradiated lymphocytes were associated with acute and late radiotherapy toxicity, using SAM, ANOVA, and t-test analyses, with raw microarray data deposited in GEO under accession GSE15341.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:19497124", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In conclusion, we have found an association between the constitutive gene expression profile of peripheral blood lymphocytes and the development of acute and late toxicity in consecutive, unselected patients."}, {"asset": "source:pmid:19497124", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Using ANOVA and t-test statistical tools we found 20 and 26 constitutive genes (0 Gy) that segregate patients with and without acute and late toxicity, respectively."}, {"asset": "source:pmid:19497124", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Raw data from microarray experiments were uploaded to the Gene Expression Omnibus Database (GEO accession GSE15341)."}, {"asset": "source:pmid:19497124", "locator": "sections[3] \"Results\" paragraph 2", "quote": "Comparison of gene expression profiles from 0 Gy and 2 Gy-treated lymphocytes, using two-class paired test in SAM program, identified a total of 81 genes significantly regulated by RT [see Additional file 2]."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The paper found that constitutive gene-expression profiles in un-irradiated lymphocytes were associated with acute and late radiotherapy toxicity, using SAM, ANOVA, and t-test analyses, with raw microarray data deposited in GEO under accession GSE15341.", "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:19497124"], "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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