Overexpression of G protein‑coupled receptor 87 correlates with poorer tumor differentiation and higher tumor proliferation in non‑small‑cell lung cancer

Nii,Kazuhito; Tokunaga,Yoshimasa; Liu,Dage; Zhang,Xia; Nakano,Jun; Ishikawa,Shinya; Kakehi,Yoshiyuki; Haba,Reiji; Yokomise,Hiroyasu

doi:10.3892/mco.2014.292

July-August 2014 Volume 2 Issue 4

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July-August 2014 Volume 2 Issue 4

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Article

Overexpression of G protein‑coupled receptor 87 correlates with poorer tumor differentiation and higher tumor proliferation in non‑small‑cell lung cancer

Authors:
- Kazuhito Nii
- Yoshimasa Tokunaga
- Dage Liu
- Xia Zhang
- Jun Nakano
- Shinya Ishikawa
- Yoshiyuki Kakehi
- Reiji Haba
- Hiroyasu Yokomise
View Affiliations / Copyright

Affiliations: Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Kagawa University, Miki, Kagawa 761‑0793, Japan, Department of Urology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761‑0793, Japan, Department of Pathology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761‑0793, Japan
Pages: 539-544
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Published online on: May 15, 2014

https://doi.org/10.3892/mco.2014.292
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Abstract

G protein‑coupled receptor 87 (GPR87) is a newly deorphanized member of the transmembrane G protein‑coupled receptor family. Recently, GPR87 was suggested to contribute to the viability of human tumor cells and overexpression of GPR87 mRNA was detected in a number of malignant tumors, including lung cancer. We performed a retrospective study of GPR87 expression in association with clinical characteristics and biological markers in non‑small‑cell lung cancer (NSCLC). We investigated a total of 123 patients with NSCLC who underwent surgery between 1999 and 2004 (58 adenocarcinomas, 53 squamous cell carcinomas and 12 others). Immunohistochemistry was used to evaluate the intratumoral expression of GPR87 and the Ki‑67 proliferation index. The TUNEL method was also used to investigate tumor apoptosis. A total of 63 tumors (51.2%) were found to be GPR87‑positive. These tumors were more frequently encountered among squamous cell carcinomas rather than among adenocarcinomas (62.3 vs. 43.1%, respectively; P=0.044) and were significantly more frequently poorly and moderately differentiated rather than well differentiated (P=0.029). Moreover, the Ki‑67 index was significantly higher in GPR87‑positive compared to GPR87‑negative tumors (57.0 vs. 40.0%, respectively; P=0.002). The overall survival was significantly worse for patients with GPR87‑positive compared to those with GPR87‑negative tumors (P=0.029). The Cox regression analyses also demonstrated that the GPR87 status was a significant prognostic factor for NSCLC patients [hazard ratio=2.053; P=0.018). The present study demonstrated that in NSCLC, the overexpression of GPR87 is significantly associated with poorer differentiation and higher proliferation. During the progression of NSCLC, GPR87 overexpression may be associated with the acquisition of a more aggressive phenotype and, therefore, is a potentially useful target for prognostication and treatment.

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1	Jemal A, Siegel R, Ward E, Hao Y, Xu J and Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 59:225–249. 2009. View Article : Google Scholar
2	Jackman DM, Miller VA, Cioffredi LA, et al: Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated non-small cell lung cancer patients: results of an online tumor registry of clinical trials. Clin Cancer Res. 15:5267–5273. 2009. View Article : Google Scholar
3	Fredriksson R, Lagerstrom MC, Lundin LG and Schioth HB: The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol Pharmacol. 63:1256–1272. 2003. View Article : Google Scholar : PubMed/NCBI
4	Pierce KL, Premont RT and Lefkowitz RJ: Seven-transmembrane receptors. Nat Rev Mol Cell Biol. 3:639–650. 2002. View Article : Google Scholar
5	Dorsam RT and Gutkind JS: G-protein-coupled receptors and cancer. Nat Rev Cancer. 7:79–94. 2007. View Article : Google Scholar : PubMed/NCBI
6	Nonaka Y, Hiramoto T and Fujita N: Identification of endogenous surrogate ligands for human P2Y12 receptors by in silico and in vitro methods. Biochem Biophys Res Commun. 337:281–288. 2005. View Article : Google Scholar : PubMed/NCBI
7	Wittenberger T, Schaller HC and Hellebrand S: An expressed sequence tag (EST) data mining strategy succeeding in the discovery of new G-protein coupled receptors. J Mol Biol. 307:799–813. 2001. View Article : Google Scholar : PubMed/NCBI
8	Tabata K, Baba K, Shiraishi A, Ito M and Fujita N: The orphan GPCR GPR87 was deorphanized and shown to be a lysophosphatidic acid receptor. Biochem Biophys Res Commun. 363:861–866. 2007. View Article : Google Scholar : PubMed/NCBI
9	Glatt S, Halbauer D, Heindl S, et al: hGPR87 contributes to viability of human tumor cells. Int J Cancer. 122:2008–2016. 2008. View Article : Google Scholar : PubMed/NCBI
10	Zhang Y, Qian Y, Lu W and Chen X: The G protein-coupled receptor 87 is necessary for p53-dependent cell survival in response to genotoxic stress. Cancer Res. 69:6049–6056. 2009. View Article : Google Scholar : PubMed/NCBI
11	Goldstraw P, Crowley J, Chansky K, et al; International Association for the Study of Lung Cancer International Staging Committee. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol. 2:706–714. 2007. View Article : Google Scholar
12	Nakano J, Huang C, Liu D, et al: Evaluations of biomarkers associated with 5-FU sensitivity for non-small-cell lung cancer patients postoperatively treated with UFT. Br J Cancer. 95:607–615. 2006. View Article : Google Scholar : PubMed/NCBI
13	Sgonc R and Wick G: Methods for the detection of apoptosis. Int Arch Allergy Immunol. 105:327–332. 1994. View Article : Google Scholar
14	Lee DK, Nguyen T, Lynch KR, et al: Discovery and mapping of ten novel G protein-coupled receptor genes. Gene. 275:83–91. 2001. View Article : Google Scholar : PubMed/NCBI
15	Gugger M, White R, Song S, et al: GPR87 is an overexpressed G-protein coupled receptor in squamous cell carcinoma of the lung. Dis Markers. 24:41–50. 2008. View Article : Google Scholar : PubMed/NCBI
16	Okazoe H, Zhang X, Liu D, et al: Expression and role of GPR87 in urothelial carcinoma of the bladder. Int J Mol Sci. 14:12367–12379. 2013. View Article : Google Scholar : PubMed/NCBI
17	Johnson JL, Pillai S and Chellappan SP: Genetic and biochemical alterations in non-small cell lung cancer. Biochem Res Int. 2012:9404052012. View Article : Google Scholar : PubMed/NCBI
18	Tammemagi MC, McLaughlin JR and Bull SB: Meta-analyses of p53 tumor suppressor gene alterations and clinicopathological features in resected lung cancers. Cancer Epidemiol Biomarkers Prev. 8:625–634. 1999.PubMed/NCBI
19	Kishimoto Y, Murakami Y, Shiraishi M, Hayashi K and Sekiya T: Aberrations of the p53 tumor suppressor gene in human non-small cell carcinomas of the lung. Cancer Res. 52:4799–4804. 1992.PubMed/NCBI
20	Mogi A and Kuwano H: TP53 mutations in nonsmall cell lung cancer. J Biomed Biotechnol. 2011:5839292011. View Article : Google Scholar : PubMed/NCBI
21	Mitsudomi T, Hamajima N, Ogawa M and Takahashi T: Prognostic significance of p53 alterations in patients with non-small cell lung cancer: a meta-analysis. Clin Cancer Res. 6:4055–4063. 2000.PubMed/NCBI
22	Zhang Y, Scoumanne A and Chen X: G protein-coupled receptor 87: a promising opportunity for cancer drug discovery. Mol Cell Pharmacol. 2:111–116. 2010.PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Overexpression of G protein‑coupled receptor 87 correlates with poorer tumor differentiation and higher tumor proliferation in non‑small‑cell lung cancer

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