Document Detail


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.
MedLine Citation:
PMID:  23154545     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
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:
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:
Created Date:  2012-11-16     Completed Date:  2013-05-07     Revised Date:  2013-09-24    
Medline Journal Info:
Nlm Unique ID:  101274235     Medline TA:  J Thorac Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1747-54     Citation Subset:  IM    
Affiliation:
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:
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:
CA-16672/CA/NCI NIH HHS; P30 CA016672/CA/NCI NIH HHS; P50 CA070907/CA/NCI NIH HHS; P50CA70907/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/GPRC5A protein, human; 0/Receptors, G-Protein-Coupled
Comments/Corrections

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