| Murine microenvironment metaprofiles associate with human cancer etiology and intrinsic subtypes. | |
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MedLine Citation:
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PMID: 23339125 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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PURPOSE: Ionizing radiation is a well established carcinogen in rodent models and a risk factor associated with human cancer. We developed a mouse model that captures radiation effects on host biology by transplanting unirradiated Trp53 null mammary tissue to sham or irradiated hosts. Gene expression profiles of tumors that arose in irradiated mice are distinct from those that arose in naïve hosts. We asked whether expression metaprofiles could discern radiation-preceded human cancer or be informative in sporadic breast cancers. EXPERIMENTAL DESIGN: Affymetrix microarray gene expression data from 56 Trp53 null mammary tumors were used to define gene profiles and a centroid that discriminate tumors arising in irradiated hosts. These were applied to publicly available human cancer data sets. RESULTS: Host irradiation induces a metaprofile consisting of gene modules representing stem cells, cell motility, macrophages and autophagy. Human orthologs of the host irradiation metaprofile discriminated between radiation-preceded and sporadic human thyroid cancers. An irradiated host centroid was strongly associated with estrogen receptor negative breast cancer. When applied to sporadic human breast cancers, the irradiated host metaprofile strongly associated with basal-like and claudin-low breast cancer intrinsic subtypes. Comparing host irradiation in the context of TGFβ levels showed that inflammation was robustly associated with claudin-low tumors. CONCLUSIONS: Detection of radiation-preceded human cancer by the irradiated host metaprofile raises possibilities of assessing human cancer etiology. Moreover, the association of the irradiated host metaprofiles with estrogen receptor negative status and claudin-low subtype suggests that host processes similar to those induced by radiation underlie sporadic cancers. |
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Authors:
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David H Nguyen; Erik Fredlund; Wei Zhao; Charles M Perou; Allan Balmain; Jian-Hua Mao; Mary Helen Barcellos-Hoff |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-21 |
Journal Detail:
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Title: Clinical cancer research : an official journal of the American Association for Cancer Research Volume: - ISSN: 1078-0432 ISO Abbreviation: Clin. Cancer Res. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9502500 Medline TA: Clin Cancer Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Radiation Oncology, New York University School of Medicine. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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