G-Protein Coupled Receptor Family C, Group 5, Member A (gprc5a) Expression Is Decreased in the Adjacent Field and Normal Bronchial Epithelia of Patients.

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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 Junya Fujimoto, MD, PhD, Humam Kadara, PhD, Melinda M. Garcia, MS, Mohamed Kabbout, PhD, Carmen Behrens, MD, Diane D. Liu, MS, J. Jack Lee, DDS, PhD, Luisa M. Solis, MD, Edward S. Kim, MD, Neda Kalhor, MD, Cesar Moran, MD, Amir Sharafkhaneh, MD, PhD, Reuben Lotan, PhD, Ignacio I. Wistuba, MD Journal of Thoracic Oncology Volume 7, Issue 12, Pages 1747-1754 (December 2012) DOI: 10.1097/JTO.0b013e31826bb1ff Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 GPRC5A immunohistochemical expression in NSCLC histological tissue specimens. A, Representative photomicrographs of GPRC5A immunohistochemical expression in lung adenocarcinoma (left) and SCC (right) observed under a light microscope at a magnification of 20 ×. Bars, 100 µm. B, Box-plots depicting differences in GPRC5A immunohistochemical expression among NBE, Adeno, and SCCs. C, Box-plots depicting GPRC5A expression based on tobacco history (never versus ever smokers), (D), smoking status (never, former and current), and (E), differentiation grade (well, moderate, and poor). p values based on the Wilcoxon rank sum test and Kruskal–Wallis test. GPRC5A, g-protein coupled receptor family C, group 5, member A; NSCLC, non–small-cell lung cancer; SCC, squamous cell carcinomas; NBE, normal bronchial epithelia; Adeno, adenocarcinomas. Journal of Thoracic Oncology 2012 7, 1747-1754DOI: (10.1097/JTO.0b013e31826bb1ff) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Reduced GPRC5A expression in the sequential pathogenesis of COPD-associated NSCLC. A, Representative photomicrographs of GPRC5A immunohistochemical expression in NBE from disease-free never and ever smokers (upper left and upper right, respectively) and in NBE from cancer-free COPD patients (bottom left) and NSCLC patients (bottom right) with COPD observed under a light microscope at a magnification of × 20. Bars, 100 µm. B, Box-plots depicting quantification of GPRC5A immunohistochemical expression represented in (A). Main p value signifies statistical significance of reduced GPRC5A expression in the sequential pathogenesis of COPD-associated NSCLC and among the five groups by the general linear model and Kruskal–Wallis test. p values signifying the indicated pair wise comparisons among the groups were obtained by the Wilcoxon rank sum test. GPRC5A, g-protein coupled receptor family C, group 5, member A; NBE, normal bronchial epithelia; NSCLC, non–small-cell lung cancer; COPD, chronic obstructive pulmonary disease; SCC, squamous cell carcinomas; NS, not significant. Journal of Thoracic Oncology 2012 7, 1747-1754DOI: (10.1097/JTO.0b013e31826bb1ff) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 Decreased GPRC5A mRNA expression in histologically NBE and corresponding NSCLC tumors from resected specimens compared with matched uninvolved normal lung. Total RNA was isolated from brushings of NBE and frozen sections of matched NSCLC (T) and uninvolved NL parenchyma obtained from resected lobectomy or pneumonectomy specimens performed on smoker early-stage patients. A, GPRC5A expression was analyzed in all samples (in triplicates) by QRTPCR and normalized against that of ACTB to yield a relative expression by the 2-△△CT method depicted in the graphs. NSCLC tumors (squamous cell carcinoma, cases 1–3, and adenocarcinomas, cases 4–6), uninvolved NL parenchyma and bronchial structures are labeled by the indicated colors. B, GPRC5A transcript expression among uninvolved NL tissue, NBE, and NSCLC tumors was assessed statistically by repeated measures analysis. NBE, normal bronchial epithelia; NSCLC, non–small-cell lung cancer; NL, normal lung; CT, comparative cycle threshold method.; QRTPCR, quantitative real-time polymerase chain reaction. Journal of Thoracic Oncology 2012 7, 1747-1754DOI: (10.1097/JTO.0b013e31826bb1ff) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions