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

Introduction: Understanding oncogenes and tumor suppressor genes expression patterns is essential for characterizing lung cancer pathogenesis. We have previously demonstrated that m Gprc5a /h GPRC5A 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 p p = 0.004) and further attenuated and lowest in epithelia of COPD patients with adenocarcinoma and SCC ( p 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.