Tumor Biology

, Volume 35, Issue 12, pp 12671–12677 | Cite as

Single-nucleotide polymorphisms of the PRKCG gene and osteosarcoma susceptibility

  • Ying Zhang
  • Xu Hu
  • Hong-Kai Wang
  • Wei-Wei Shen
  • Tong-Quan Liao
  • Pei Chen
  • Tong-Wei Chu
Research Article


The objective of this study was to explore the relationship between single-nucleotide polymorphisms (SNPs) of the protein kinase C gamma (PRKCG) gene and osteosarcoma susceptibility in Chinese Han population. A total of 610 cases of osteosarcoma patients and 610 healthy individuals were enrolled in this study. TaqMan method was used to compare genotypes and the allelic distribution frequency of three SNPs (rs454006, rs2242245, and rs8103851) in the PRKGG gene between osteosarcoma patients and healthy individuals. Osteosarcoma patients were grouped according to different clinical parameters (age, gender, pathological types, tumor location, Enneking staging, tumor metastasis and treatment) to compare genotype and allele frequency among different groups as well as to explore the relationship between gene polymorphisms and different clinical parameters. The rs454006 polymorphisms of the PRKCG gene include the CC, CT, and TT genotypes. The differences in genotype frequency and allele frequency between osteosarcoma patients and healthy individuals were significant (both P < 0.001). There was no significant different between osteosarcoma patients and healthy individuals in rs8103851 and rs2242245 polymorphisms of the PRKCG gene (both P > 0.05). The differences of the rs8103851 genotype frequency and allele frequency in patients with metastatic osteosarcoma and patients without metastasis were significant (both P < 0.001). The distribution frequencies of the CG and GG genotypes as well as the G allele in patients with metastatic osteosarcoma were higher than in patients without metastasis. The genotype frequency and allele frequency of rs454006 and rs2242245 did not correlate with clinical parameters. The rs454006 polymorphism of the PRKCG gene correlated to osteosarcoma susceptibility and might increase the risk of osteosarcoma. The rs8103851 correlated to metastatic osteosarcoma and could be risk factors for metastatic osteosarcoma.


Osteosarcoma Protein kinase C Polymorphism Single nucleotide Disease susceptibility 



The research was supported by the National Science Foundation (Grant No. 81271979).


  1. 1.
    Campanacci M. Bone and soft tissue tumors: clinical features, imaging, pathology and treatment. New York: Springer; 1999. p. 464–91.CrossRefGoogle Scholar
  2. 2.
    Stiller CA, Bielack SS, Jundt G, et al. Bone tumours in European children and adolescents,1978–1997, report from the Automated Childhood Cancer Information System project. Eur J Cancer. 2006;42(2124).Google Scholar
  3. 3.
    Haddox CL, Han G, Anijar L, et al. Osteosarcoma in pediatric patients and young adults: a single institution retrospective review of presentation, therapy, and outcome. Sarcoma. 2014;2014:402509.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Wafa H, Grimer RJ. Surgical options and outcomes in bone sarcoma. Expert Rev Anticancer Ther. 2006;6:239–48.PubMedCrossRefGoogle Scholar
  5. 5.
    Meyers PA, Schwartz CL, Krailo MD, et al. Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival—a report from the Children's Oncology Group. J Clin Oncol. 2008;26:633–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Hawkins MM, Wilson LMK, Burton HS, et al. Radiotherapy, alkylating agents, and risk of bone cancer after childhood cancer. J Natl Cancer Inst. 1996;88:270–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Zhong GQ, Tu RH, Zeng ZY, et al. Novel functional role of heat shock protein 90 in protein kinase C-mediated ischemic postconditioning. J Surg Res. 2014;189:198–206.PubMedCrossRefGoogle Scholar
  8. 8.
    Klebe S, Durr A, Rentschler A, et al. New mutations in protein kinase C gamma associated with spinocerebellar ataxia type 14. Ann Neurol. 2005;58:720–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Mochizuki H, Seki T, Adachi N, et al. R659S mutation of γPKC is susceptible to cell death: implication of this mutation/polymerp-hism in the pathogenesis of retinitis pigmentosa. Neurochem Int. 2006;49:669–75.PubMedCrossRefGoogle Scholar
  10. 10.
    Parsons M, Adams JC. Rac regulates the interaction of fascin with protein kinase C in cell migration. J Cell Sci. 2008;121:2805–13.PubMedCrossRefGoogle Scholar
  11. 11.
    Mazzoni E, Adam A, Bal de Kier Joffe E, et al. Immortalized mammary epithelial cells overexpressing protein kinase C gamma acquire a malignant phenotype and become tumorigenic in vivo. Mol Cancer Res. 2003;1:776–87.PubMedGoogle Scholar
  12. 12.
    Xie X, Ma YT, Fu ZY, Yang YN, Ma X, Chen BD, et al. Haplotype analysis of the CYP8A1 gene associated with myocardial infarction. Clin Appl Thromb Hemost. 2009;15:574–80.CrossRefGoogle Scholar
  13. 13.
    Shi YY, He L. SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res. 2005;15:97–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Li Z, Zhang Z, He Z, et al. A partition-ligation-combination-subdivision EM algorithm for haplotype inference with multiallelic markers: update of the SHEsis ( Cell Res. 2009;19:519–23.PubMedCrossRefGoogle Scholar
  15. 15.
    Chen C, Kano M, Abeliovich A, et al. Impaired motor-coordination correlates with persistent multiple climbing fiber innervation in PKC gamma mutant mice. Cell. 1995;83:1233–42.PubMedCrossRefGoogle Scholar
  16. 16.
    Nolte D, Landendinger M, Schmitt E, et al. Spinocerebellar ataxia 14: novel mutation in exon 2 of PRKCG in a German family. Mov Disord. 2007;22:265–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Fahey MC, Knight MA, Shaw JH, et al. Spinocerebellar ataxia type 14: study of a family with an exon 5 mutation in the PRKCG gene. J Neurol Neurosurg Psychiatry. 2005;76:1720–2.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Hashimoto Y, Parsons M, Adams JC. Dual actin-bundling and protein kinase C-binding activities of fascin regulate carcinoma cell migration downstream of Rac and contribute to metastasis. Mol Biol Cell. 2007;18:4591–602.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Vignjevic D, Schoumacher M, Gavert N, et al. Fascin, a novel target of beta-catenin-TCF signaling, is expressed at the invasive front of human colon cancer. Cancer Res. 2007;67:6844–53.PubMedCrossRefGoogle Scholar
  20. 20.
    Li Y, Dang TA, Shen J, et al. Identification of a plasma proteomic signature to distinguish pediatric osteosarcoma from benign osteochondroma. Proteomics. 2006;6:3426–35.PubMedCrossRefGoogle Scholar
  21. 21.
    Ren L, Hong SH, Cassavaugh J, et al. The actin-cytoskeleton linker protein ezrin is regulated during osteosarcoma metastasis by PKC. Oncogene. 2008;28:792–802.PubMedCrossRefGoogle Scholar
  22. 22.
    Koivunen J, Aaltonen V, Koskela S, et al. Protein kinase C α/β inhibitor Go6976 promotes formation of cell junctions and inhibits invasion of urinary bladder carcinoma cells. Cancer Res. 2004;64:5693–701.PubMedCrossRefGoogle Scholar
  23. 23.
    Taylor J, Pampillo M, Bhattacharya M, Babwah AV. Kisspeptin/KISS1R signaling potentiates extravillous trophoblast adhesion to type-I collagen in a PKC- and ERK1/2-dependent manner. Mol Reprod Dev. 2014;81:42–54.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Ying Zhang
    • 1
  • Xu Hu
    • 1
  • Hong-Kai Wang
    • 1
  • Wei-Wei Shen
    • 1
  • Tong-Quan Liao
    • 1
  • Pei Chen
    • 1
  • Tong-Wei Chu
    • 1
  1. 1.Department of Orthopaedics, Xinqiao HospitalThe Third Military Medical UniversityChongqingChina

Personalised recommendations