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Tumor Biology

, Volume 37, Issue 1, pp 1105–1112 | Cite as

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

  • Kun Wang
  • Jinmin Zhao
  • Maolin He
  • Mitra Fowdur
  • Tenglong Jiang
  • Shuju Luo
Original Article

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.

Keywords

Osteosarcoma GRM4 Single nucleotide polymorphism Clinicopathological characteristics 

Notes

Acknowledgments

This research was supported by the National Natural Science Foundation of China (Grant No. 81460407) and the Guangxi Science Funds of China (Grant No. 2012GXNSFAA053087).

Conflicts of interest

None

References

  1. 1.
    Ando K, Heymann M-F, Stresing V, Rédini KMF, Heymann D. Current therapeutic strategies and novel approaches in osteosarcoma. Cancers. 2013;5:591–616.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    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.CrossRefPubMedGoogle Scholar
  3. 3.
    Moore DD, Luu HH. Osteosarcoma. Cancer Treat Res. 2014;162:65–92.CrossRefPubMedGoogle Scholar
  4. 4.
    Ottaviani G, Jaffe N. The etiology of osteosarcoma. Cancer Treat Res. 2009;152:15–32.CrossRefPubMedGoogle Scholar
  5. 5.
    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.CrossRefPubMedGoogle Scholar
  6. 6.
    Gorlick R. Current concepts on the molecular biology of osteosarcoma. Cancer Treat Res. 2009;152:467–78.CrossRefPubMedGoogle Scholar
  7. 7.
    Liu Y, Lv B, He Z, Zhou Y, Han C, Shi G, et al. Lysyl oxidase polymorphisms and susceptibility to osteosarcoma. PLoS One. 2012;7(7), e41610.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    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.PubMedGoogle Scholar
  9. 9.
    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.CrossRefPubMedGoogle Scholar
  10. 10.
    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.CrossRefPubMedGoogle Scholar
  11. 11.
    Skerry TM, Genever PG. Glutamate signalling in non-neuronal tissues. Trends Pharmacol Sci. 2001;22(4):174–81.CrossRefPubMedGoogle Scholar
  12. 12.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Skerry T. The role of glutamate in the regulation of bone mass and architecture. J Musculoskelet Neuronal Interact. 2008;8(2):166–73.PubMedGoogle Scholar
  15. 15.
    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.PubMedGoogle Scholar
  16. 16.
    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.CrossRefPubMedGoogle Scholar
  17. 17.
    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.CrossRefPubMedGoogle Scholar
  18. 18.
    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.CrossRefPubMedGoogle Scholar
  19. 19.
    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.CrossRefPubMedGoogle Scholar
  20. 20.
    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.PubMedGoogle Scholar
  21. 21.
    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.CrossRefPubMedGoogle Scholar
  22. 22.
    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.CrossRefPubMedGoogle Scholar
  23. 23.
    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.CrossRefPubMedGoogle Scholar
  24. 24.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    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.CrossRefPubMedGoogle Scholar
  28. 28.
    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.CrossRefPubMedGoogle Scholar
  29. 29.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    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.CrossRefPubMedGoogle Scholar
  31. 31.
    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.CrossRefGoogle Scholar
  32. 32.
    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.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Kun Wang
    • 1
    • 2
  • Jinmin Zhao
    • 2
    • 3
  • Maolin He
    • 1
    • 2
  • Mitra Fowdur
    • 1
    • 2
  • Tenglong Jiang
    • 1
    • 2
  • Shuju Luo
    • 1
    • 2
  1. 1.Division of Spinal SurgeryThe First Affiliated Hospital of Guangxi Medical UniversityNanningChina
  2. 2.Guangxi Key Laboratory of Regenerative MedicineGuangxi Medical UniversityNanningChina
  3. 3.Department of Orthopedic Trauma and Hand SurgeryThe First Affiliated Hospital of Guangxi Medical UniversityNanningChina

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