| G-protein coupled receptor family C, group 5, member A (GPRC5A) expression is decreased in the adjacent field and normal bronchial epithelia of patients with chronic obstructive pulmonary disease and non-small-cell lung cancer. | |
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MedLine Citation:
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PMID: 23154545 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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INTRODUCTION: Understanding oncogenes and tumor suppressor genes expression patterns is essential for characterizing lung cancer pathogenesis. We have previously demonstrated that mGprc5a/hGPRC5A is a lung-specific tumor suppressor evidenced by inflammation-mediated tumorigenesis in Gprc5a-knockout mice. The implication of GPRC5A in human lung cancer pathogenesis, including that associated with inflammatory chronic obstructive pulmonary disease (COPD), a risk factor for the malignancy, remains elusive. METHODS: We sought to examine GPRC5A immunohistochemical expression in histologically normal bronchial epithelia (NBE) from lung disease-free never- and ever-smokers (n = 13 and n = 18, respectively), from COPD patients with (n = 26) and without cancer (n = 24) and in non-small cell lung cancers (NSCLCs) (n = 474). Quantitative assessment of GPRC5A transcript expression in airways (n = 6), adjacent NBEs (n = 29) and corresponding tumors (n = 6) from 6 NSCLC patients was also performed. RESULTS: GPRC5A immunohistochemical expression was significantly lower in tumors compared to uninvolved NBE (p < 0.0001) and was positively associated with adenocarcinoma histology (p < 0.001). GPRC5A airway expression was highest in lung disease-free NBE, decreased and intermediate in NBE of cancer-free COPD patients (p = 0.004) and further attenuated and lowest in epithelia of COPD patients with adenocarcinoma and SCC (p < 0.0001). Furthermore, GPRC5A mRNA was significantly decreased in NSCLCs and corre sponding NBE compared to uninvolved normal lung (p = 0.03). CONCLUSIONS: Our findings highlight decreased GPRC5A expression in the field cancerization of NSCLC, including that associated with lung inflammation. Assessment of the use of GPRC5A expression as a risk factor for NSCLC development in COPD patients is warranted. |
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Authors:
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Junya Fujimoto; Humam Kadara; Melinda M Garcia; Mohamed Kabbout; Carmen Behrens; Diane D Liu; J Jack Lee; Luisa M Solis; Edward S Kim; Neda Kalhor; Cesar Moran; Amir Sharafkhaneh; Reuben Lotan; Ignacio I Wistuba |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer Volume: 7 ISSN: 1556-1380 ISO Abbreviation: J Thorac Oncol Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-11-16 Completed Date: 2013-05-07 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 101274235 Medline TA: J Thorac Oncol Country: United States |
Other Details:
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Languages: eng Pagination: 1747-54 Citation Subset: IM |
Affiliation:
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Department of Thoracic/Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. jfujimot@mdanderson.org |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenocarcinoma
/
genetics,
metabolism,
pathology Bronchi / metabolism*, pathology Carcinoma, Non-Small-Cell Lung / genetics, metabolism*, pathology Carcinoma, Squamous Cell / genetics, metabolism, pathology Female Humans Immunoenzyme Techniques Lung Neoplasms / genetics, metabolism*, pathology Male Middle Aged Neoplasm Grading Neoplasm Staging Pneumonia / genetics, metabolism, pathology Prognosis Pulmonary Disease, Chronic Obstructive / genetics, metabolism*, pathology Receptors, G-Protein-Coupled / genetics, metabolism* Respiratory Mucosa / metabolism*, pathology |
| Grant Support | |
ID/Acronym/Agency:
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CA-16672/CA/NCI NIH HHS; P50 CA070907/CA/NCI NIH HHS; P50CA70907/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/GPRC5A protein, human; 0/Receptors, G-Protein-Coupled |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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