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Erschienen in: Tumor Biology 1/2016

15.08.2015 | Original Article

Association of GRM4 gene polymorphisms with susceptibility and clinicopathological characteristics of osteosarcoma in Guangxi Chinese population

verfasst von: Kun Wang, Jinmin Zhao, Maolin He, Mitra Fowdur, Tenglong Jiang, Shuju Luo

Erschienen in: Tumor Biology | Ausgabe 1/2016

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Abstract

Osteosarcoma is the most frequent malignant primary bone tumor. GRM4 is expressed in human osteosarcoma cells, and high expression of mGluR4 in osteosarcoma tissues is related to poor prognosis. The aim of this study was to investigate the association between polymorphism of the GRM4 gene and the susceptibility to osteosarcoma in a Chinese population. In a case–control study, we investigated polymorphisms in the GRM4 gene (rs2229901, rs733457, and rs1906953) with a real-time quantitative polymerase chain reaction (PCR) assay (TaqMan). The study was conducted with 126 Chinese patients with osteosarcoma and 168 Chinese subjects in a control group. Unconditional logistic regression was used to analyze the correlation between single nucleotide polymorphisms (SNPs) and osteosarcoma risk. Different survival rates of different genotypic patients with osteosarcoma were analyzed through Kaplan–Meier. There were statistically significant differences in the distributions of the rs1906953 genotypes between the cases and control group (P = 0.034). However, there was no remarkable difference in the three genotypes of GRM4 gene rs2229901 locus between the patient group and control group (P = 0.369). Survival analysis for rs1906953 showed that the median survival time of osteosarcoma patients with the CC genotype was significantly shorter compared to the CT and TT genotypes; patients carrying CC genotype have apparently got a decrease in their recurrence-free survival time in comparison with patients carrying TT genotype. Our data suggest that GRM4 gene polymorphism is closely related to the morbidity and metastasis of osteosarcoma in a Chinese population.
Literatur
1.
Zurück zum Zitat Ando K, Heymann M-F, Stresing V, Rédini KMF, Heymann D. Current therapeutic strategies and novel approaches in osteosarcoma. Cancers. 2013;5:591–616.CrossRefPubMedPubMedCentral Ando K, Heymann M-F, Stresing V, Rédini KMF, Heymann D. Current therapeutic strategies and novel approaches in osteosarcoma. Cancers. 2013;5:591–616.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Fuchs B, Zhang K, Schabel A, Bolander ME, Sarkar G. Identification of twenty-two candidate markers for human osteogenic sarcoma. Gene. 2001;278(1–2):245–52.CrossRefPubMed Fuchs B, Zhang K, Schabel A, Bolander ME, Sarkar G. Identification of twenty-two candidate markers for human osteogenic sarcoma. Gene. 2001;278(1–2):245–52.CrossRefPubMed
4.
5.
Zurück zum Zitat Bielack SS, Kempf-Bielack B, Branscheid D, Carrle D, Friedel G, Helmke K, et al. Second and subsequent recurrences of osteosarcoma: presentation, treatment, and outcomes of 249 consecutive cooperative osteosarcoma study group patients. J Clin Oncol. 2009;27(4):557–65.CrossRefPubMed Bielack SS, Kempf-Bielack B, Branscheid D, Carrle D, Friedel G, Helmke K, et al. Second and subsequent recurrences of osteosarcoma: presentation, treatment, and outcomes of 249 consecutive cooperative osteosarcoma study group patients. J Clin Oncol. 2009;27(4):557–65.CrossRefPubMed
6.
Zurück zum Zitat Gorlick R. Current concepts on the molecular biology of osteosarcoma. Cancer Treat Res. 2009;152:467–78.CrossRefPubMed Gorlick R. Current concepts on the molecular biology of osteosarcoma. Cancer Treat Res. 2009;152:467–78.CrossRefPubMed
7.
8.
Zurück zum Zitat Pissimissis N, Papageorgiou E, Lembessis P, Armakolas A, Koutsilieris M. The glutamatergic system expression in human PC-3 and LNCaP prostate cancer cells. Anticancer Res. 2009;29(1):371–7.PubMed Pissimissis N, Papageorgiou E, Lembessis P, Armakolas A, Koutsilieris M. The glutamatergic system expression in human PC-3 and LNCaP prostate cancer cells. Anticancer Res. 2009;29(1):371–7.PubMed
9.
Zurück zum Zitat Takano T, Lin JH, Arcuino G, Gao Q, Yang J, Nedergaard M, et al. Glutamate release promotes growth of malignant gliomas. Nat Med. 2001;7(9):1010–5.CrossRefPubMed Takano T, Lin JH, Arcuino G, Gao Q, Yang J, Nedergaard M, et al. Glutamate release promotes growth of malignant gliomas. Nat Med. 2001;7(9):1010–5.CrossRefPubMed
10.
Zurück zum Zitat Aramori I, Nakanishi S. Signal transduction and pharmacological characteristics of a metabotropic glutamate receptor, mGluR1, in transfected CHO cells. Neuron. 1992;8(4):757–65.CrossRefPubMed Aramori I, Nakanishi S. Signal transduction and pharmacological characteristics of a metabotropic glutamate receptor, mGluR1, in transfected CHO cells. Neuron. 1992;8(4):757–65.CrossRefPubMed
11.
Zurück zum Zitat Skerry TM, Genever PG. Glutamate signalling in non-neuronal tissues. Trends Pharmacol Sci. 2001;22(4):174–81.CrossRefPubMed Skerry TM, Genever PG. Glutamate signalling in non-neuronal tissues. Trends Pharmacol Sci. 2001;22(4):174–81.CrossRefPubMed
12.
Zurück zum Zitat Molyneux SD, Di Grappa MA, Beristain AG, McKee TD, Wai DH, Paderova J, et al. Prkar1a is an osteosarcoma tumor suppressor that defines a molecular subclass in mice. J Clin Investig. 2010;120(9):3310–25.CrossRefPubMedPubMedCentral Molyneux SD, Di Grappa MA, Beristain AG, McKee TD, Wai DH, Paderova J, et al. Prkar1a is an osteosarcoma tumor suppressor that defines a molecular subclass in mice. J Clin Investig. 2010;120(9):3310–25.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Griffin KJ, Kirschner LS, Matyakhina L, Stergiopoulos SG, Robinson-White A, Lenherr SM, et al. A transgenic mouse bearing an antisense construct of regulatory subunit type 1A of protein kinase A develops endocrine and other tumours: comparison with Carney complex and other PRKAR1A induced lesions. J Med Genet. 2004;41(12):923–31.CrossRefPubMedPubMedCentral Griffin KJ, Kirschner LS, Matyakhina L, Stergiopoulos SG, Robinson-White A, Lenherr SM, et al. A transgenic mouse bearing an antisense construct of regulatory subunit type 1A of protein kinase A develops endocrine and other tumours: comparison with Carney complex and other PRKAR1A induced lesions. J Med Genet. 2004;41(12):923–31.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Skerry T. The role of glutamate in the regulation of bone mass and architecture. J Musculoskelet Neuronal Interact. 2008;8(2):166–73.PubMed Skerry T. The role of glutamate in the regulation of bone mass and architecture. J Musculoskelet Neuronal Interact. 2008;8(2):166–73.PubMed
15.
Zurück zum Zitat Kalariti N, Lembessis P, Koutsilieris M. Characterization of the glutametergic system in MG-63 osteoblast-like osteosarcoma cells. Anticancer Res. 2004;24(6):3923–9.PubMed Kalariti N, Lembessis P, Koutsilieris M. Characterization of the glutametergic system in MG-63 osteoblast-like osteosarcoma cells. Anticancer Res. 2004;24(6):3923–9.PubMed
16.
Zurück zum Zitat Yang W, Maolin H, Jinmin Z, Zhe W. High expression of metabotropic glutamate receptor 4: correlation with clinicopathologic characteristics and prognosis of osteosarcoma. J Cancer Res Clin Oncol. 2014;140(3):419–26.CrossRefPubMed Yang W, Maolin H, Jinmin Z, Zhe W. High expression of metabotropic glutamate receptor 4: correlation with clinicopathologic characteristics and prognosis of osteosarcoma. J Cancer Res Clin Oncol. 2014;140(3):419–26.CrossRefPubMed
17.
Zurück zum Zitat Chang H, Yoo BC, Lim SB, Jeong SY, Kim WH, Park JG. Metabotropic glutamate receptor 4 expression in colorectal carcinoma and its prognostic significance. Clin Cancer Res. 2005;11(9):3288–95.CrossRefPubMed Chang H, Yoo BC, Lim SB, Jeong SY, Kim WH, Park JG. Metabotropic glutamate receptor 4 expression in colorectal carcinoma and its prognostic significance. Clin Cancer Res. 2005;11(9):3288–95.CrossRefPubMed
18.
Zurück zum Zitat Brocke KS, Staufner C, Luksch H, Geiger KD, Stepulak A, Marzahn J, et al. Glutamate receptors in pediatric tumors of the central nervous system. Cancer Biol Ther. 2010;9(6):455–68.CrossRefPubMed Brocke KS, Staufner C, Luksch H, Geiger KD, Stepulak A, Marzahn J, et al. Glutamate receptors in pediatric tumors of the central nervous system. Cancer Biol Ther. 2010;9(6):455–68.CrossRefPubMed
19.
Zurück zum Zitat Stepulak A, Luksch H, Gebhardt C, Uckermann O, Marzahn J, Sifringer M, et al. Expression of glutamate receptor subunits in human cancers. Histochem Cell Biol. 2009;132(4):435–45.CrossRefPubMed Stepulak A, Luksch H, Gebhardt C, Uckermann O, Marzahn J, Sifringer M, et al. Expression of glutamate receptor subunits in human cancers. Histochem Cell Biol. 2009;132(4):435–45.CrossRefPubMed
20.
Zurück zum Zitat Luksch H, Uckermann O, Stepulak A, Hendrusch S, Marzahn J, Bastian S, et al. Silencing of selected glutamate receptor subunits modulates cancer growth. Anticancer Res. 2011;31(10):3181–92.PubMed Luksch H, Uckermann O, Stepulak A, Hendrusch S, Marzahn J, Bastian S, et al. Silencing of selected glutamate receptor subunits modulates cancer growth. Anticancer Res. 2011;31(10):3181–92.PubMed
21.
Zurück zum Zitat Shibata H, Tani A, Chikuhara T, Kikuta R, Sakai M, Ninomiya H, et al. Association study of polymorphisms in the group III metabotropic glutamate receptor genes, GRM4 and GRM7, with schizophrenia. Psychiatry Res. 2009;167(1–2):88–96.CrossRefPubMed Shibata H, Tani A, Chikuhara T, Kikuta R, Sakai M, Ninomiya H, et al. Association study of polymorphisms in the group III metabotropic glutamate receptor genes, GRM4 and GRM7, with schizophrenia. Psychiatry Res. 2009;167(1–2):88–96.CrossRefPubMed
22.
Zurück zum Zitat Muhle H, von Spiczak S, Gaus V, Kara S, Helbig I, Hampe J, et al. Role of GRM4 in idiopathic generalized epilepsies analysed by genetic association and sequence analysis. Epilepsy Res. 2010;89(2–3):319–26.CrossRefPubMed Muhle H, von Spiczak S, Gaus V, Kara S, Helbig I, Hampe J, et al. Role of GRM4 in idiopathic generalized epilepsies analysed by genetic association and sequence analysis. Epilepsy Res. 2010;89(2–3):319–26.CrossRefPubMed
23.
Zurück zum Zitat Parihar R, Mishra R, Singh SK, Jayalakshmi S, Mehndiratta MM, Ganesh S. Association of the GRM4 gene variants with juvenile myoclonic epilepsy in an Indian population. J Genet. 2014;93(1):193–7.CrossRefPubMed Parihar R, Mishra R, Singh SK, Jayalakshmi S, Mehndiratta MM, Ganesh S. Association of the GRM4 gene variants with juvenile myoclonic epilepsy in an Indian population. J Genet. 2014;93(1):193–7.CrossRefPubMed
24.
Zurück zum Zitat Shi J, Badner JA, Hattori E, Potash JB, Willour VL, McMahon FJ, et al. Neurotransmission and bipolar disorder: a systematic family-based association study. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(7):1270–7.CrossRefPubMedPubMedCentral Shi J, Badner JA, Hattori E, Potash JB, Willour VL, McMahon FJ, et al. Neurotransmission and bipolar disorder: a systematic family-based association study. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(7):1270–7.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Savage SA, Mirabello L, Wang Z, et al. Genome-wide association study identifies two susceptibility loci for osteosarcoma. Nat Genet. 2013;45(7):799–803.CrossRefPubMedPubMedCentral Savage SA, Mirabello L, Wang Z, et al. Genome-wide association study identifies two susceptibility loci for osteosarcoma. Nat Genet. 2013;45(7):799–803.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Jiang C, Chen H, Shao L, Dong Y. GRM4 gene polymorphism is associated with susceptibility and prognosis of osteosarcoma in a Chinese Han population. Med Oncol. 2014;31(7):50.CrossRefPubMedPubMedCentral Jiang C, Chen H, Shao L, Dong Y. GRM4 gene polymorphism is associated with susceptibility and prognosis of osteosarcoma in a Chinese Han population. Med Oncol. 2014;31(7):50.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Naumov VA, Generozov EV, Solovyov YN, Aliev MD, Kushlinsky NE. Association of FGFR3 and MDM2 gene nucleotide polymorphisms with bone tumors. Bull Exp Biol Med. 2012;153(6):869–73.CrossRefPubMed Naumov VA, Generozov EV, Solovyov YN, Aliev MD, Kushlinsky NE. Association of FGFR3 and MDM2 gene nucleotide polymorphisms with bone tumors. Bull Exp Biol Med. 2012;153(6):869–73.CrossRefPubMed
28.
Zurück zum Zitat Zhang Y, Hu X, Wang HK, Shen WW, Liao TQ, Chen P, et al. Single-nucleotide polymorphisms of the PRKCG gene and osteosarcoma susceptibility. Tumour Biol. 2014;35(12):12671–7.CrossRefPubMed Zhang Y, Hu X, Wang HK, Shen WW, Liao TQ, Chen P, et al. Single-nucleotide polymorphisms of the PRKCG gene and osteosarcoma susceptibility. Tumour Biol. 2014;35(12):12671–7.CrossRefPubMed
29.
Zurück zum Zitat Caronia D, Patino-Garcia A, Perez-Martinez A, Pita G, Moreno LT, Zalacain-Diez M, et al. Effect of ABCB1 and ABCC3 polymorphisms on osteosarcoma survival after chemotherapy: a pharmacogenetic study. PLoS One. 2011;6(10), e26091.CrossRefPubMedPubMedCentral Caronia D, Patino-Garcia A, Perez-Martinez A, Pita G, Moreno LT, Zalacain-Diez M, et al. Effect of ABCB1 and ABCC3 polymorphisms on osteosarcoma survival after chemotherapy: a pharmacogenetic study. PLoS One. 2011;6(10), e26091.CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Liu S, Yi Z, Ling M, Shi J, Qiu Y, Yang S. Predictive potential of ABCB1, ABCC3, and GSTP1 gene polymorphisms on osteosarcoma survival after chemotherapy. Tumour Biol. 2014;35(10):9897–904.CrossRefPubMed Liu S, Yi Z, Ling M, Shi J, Qiu Y, Yang S. Predictive potential of ABCB1, ABCC3, and GSTP1 gene polymorphisms on osteosarcoma survival after chemotherapy. Tumour Biol. 2014;35(10):9897–904.CrossRefPubMed
31.
Zurück zum Zitat Iacovelli L, Arcella A, Battaglia G, Pazzaglia S, Aronica E, Spinsanti P, et al. Pharmacological activation of mGlu4 metabotropic glutamate receptors inhibits the growth of medulloblastomas. J Neurosci Off J Soc Neurosci. 2006;26(32):8388–97.CrossRef Iacovelli L, Arcella A, Battaglia G, Pazzaglia S, Aronica E, Spinsanti P, et al. Pharmacological activation of mGlu4 metabotropic glutamate receptors inhibits the growth of medulloblastomas. J Neurosci Off J Soc Neurosci. 2006;26(32):8388–97.CrossRef
32.
Zurück zum Zitat Fallin MD, Lasseter VK, Avramopoulos D, Nicodemus KK, Wolyniec PS, McGrath JA, et al. Bipolar I disorder and schizophrenia: a 440-single-nucleotide polymorphism screen of 64 candidate genes among Ashkenazi Jewish case-parent trios. Am J Hum Genet. 2005;77(6):918–36.CrossRefPubMedPubMedCentral Fallin MD, Lasseter VK, Avramopoulos D, Nicodemus KK, Wolyniec PS, McGrath JA, et al. Bipolar I disorder and schizophrenia: a 440-single-nucleotide polymorphism screen of 64 candidate genes among Ashkenazi Jewish case-parent trios. Am J Hum Genet. 2005;77(6):918–36.CrossRefPubMedPubMedCentral
Metadaten
Titel
Association of GRM4 gene polymorphisms with susceptibility and clinicopathological characteristics of osteosarcoma in Guangxi Chinese population
verfasst von
Kun Wang
Jinmin Zhao
Maolin He
Mitra Fowdur
Tenglong Jiang
Shuju Luo
Publikationsdatum
15.08.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 1/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3904-2

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