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Biochemical Genetics

, Volume 55, Issue 4, pp 322–334 | Cite as

Comparison of Selected Protein Levels in Tumour and Surgical Margin in a Group of Patients with Oral Cavity Cancer

  • Joanna Katarzyna StrzelczykEmail author
  • Karolina Gołąbek
  • Piotr Cuber
  • Łukasz Krakowczyk
  • Aleksander Jerzy Owczarek
  • Martyna Fronczek
  • Piotr Choręża
  • Edyta Hudziec
  • Zofia Ostrowska
Original Article
  • 244 Downloads

Abstract

Oral cavity cancer belongs to head-and-neck squamous cell carcinoma group. The purpose of the study was to assess the levels of certain proteins in a tumour and surgical margin in a group of patients with oral cavity cancer. The levels of DAPK1, MGMT, CDH1, SFRP1, SFRP2, RORA, TIMP3, p16, APC and RASSF1 proteins were measured by ELISA in tissue homogenates. The protein levels of DAPK1, MGMT, CDH1, SFRP2 and RASSF1 were significantly higher in tumour tissue than in the margin, contrary to TIMP3 which was lower in the tumour itself. DAPK1 level in the tumour was significantly higher in females than in males, the MGMT and p16 levels were lower in the tumours with lymph node metastasis (N1 + N2) than in N0 samples. The CDH1 expression was higher in a group with smoking habits, whereas TIMP3 was lower in this group. Changes in the levels of proteins in tumour and surgical margin may be either reflective of tumour occurrence and development, or they might be also responsible for the progress and reoccurrence of the disease. Levels of the studied proteins might be good prognostic factors; however, further studies are required.

Keywords

Protein level Tumour Surgical margin Cancerogenesis Oral cavity 

Notes

Acknowledgements

The study was based on personal academic funds without any support from external organisations or companies.

Compliance with Ethical Standards

Conflict of interest

The authors declare no conflict of interest.

References

  1. Ayed-Guerfali D, Hassairi B, Khabir A et al (2014) Expression of APC, β-catenin and E-cadherin in Tunisian patients with gastric adenocarcinoma: clinical significance. Tumour Biol 35:1775–1783CrossRefPubMedGoogle Scholar
  2. Bartsch D, Shevlin D, Tung W et al (1995) Frequent mutations of CDKN2 in primary pancreatic adenocarcinomas. Genes Chromosomes Cancer 14:189–195CrossRefPubMedGoogle Scholar
  3. Benderska N, Schneider-Stock R (2014) Transcription control of DAPK. Apoptosis 19:298–305CrossRefPubMedGoogle Scholar
  4. Bidaud P, Chasle J, Sichel F et al (2010) Expression of p53 family members and CD44 in oral squamous cell carcinoma (OSCC) in relation to tumorigenesis. Histol Histopathol 25:331–339PubMedGoogle Scholar
  5. Brunner M, Ng BC, Veness MJ et al (2014) Comparison of the AJCC N staging system in mucosal and cutaneous squamous head and neck cancer. Laryngoscope 124:1598–1602CrossRefPubMedGoogle Scholar
  6. Chen HY, Lee YR, Chen RH (2014) The functions and regulations of DAPK in cancer metastasis. Apoptosis 19:364–370CrossRefPubMedGoogle Scholar
  7. Chou SE, Huang CY, Sheen-Chen SM et al (2011) An evaluation of prognostic value of death-associated protein kinase 1 in breast cancer. Anticancer Res 31:3633–3636PubMedGoogle Scholar
  8. Cobanoglu U, Ersoz S, Turgutalp H et al (2004) Correlation of E-cadherin expression with clinicopathological parameters in breast carcinoma. Saudi Med J 25:1024–1027PubMedGoogle Scholar
  9. Darnton SJ, Hardie LJ, Muc RS et al (2005) Tissue inhibitor of metalloproteinase-3 (TIMP-3) gene is methylated in the development of esophageal adenocarcinoma: loss of expression correlates with poor prognosis. Int J Cancer 115:351–358CrossRefPubMedGoogle Scholar
  10. Demokan S, Chuang A, Suoğlu Y et al (2012) Promoter methylation and loss of p16(INKa) gene expression in head and neck cancer. Head Neck 34:1470–1475CrossRefPubMedGoogle Scholar
  11. Du J, Xu R (2012) RORα, a potential tumor suppressor and therapeutic target of breast cancer. Int J Mol Sci 13:15755–15766CrossRefPubMedPubMedCentralGoogle Scholar
  12. Fenton S, Dallol A, Agathanggelou A et al (2004) Identification of the E1A-Regulated transcription factor p120E4F as an interacting partner of the RASSF1A candidate tumor suppressor gene. Cancer Res 64:102–107CrossRefPubMedGoogle Scholar
  13. Fischer C, Kampmann M, Zlobec I et al (2010) p16 expression in oropharyngeal cancer: its impact on staging and prognosis compared with the conventional clinical staging parameters. Ann Oncol 21:1961–1966CrossRefPubMedGoogle Scholar
  14. Fu RD, Qiu CH, Chen HA et al (2014) Retinoic acid receptor-related receptor alpha (RORalpha) is a prognostic marker for hepatocellular carcinoma. Tumour Biol 35:7603–7610CrossRefPubMedGoogle Scholar
  15. Fuchs SY, Ougolkov AV, Spiegelman VS et al (2005) Oncogenic beta-catenin signaling networks in colorectal cancer. Cell Cycle 4:1522–1539CrossRefPubMedGoogle Scholar
  16. Gozuacik D, Kimchi A (2006) DAPk protein family and cancer. Autophagy 2:74–79CrossRefPubMedGoogle Scholar
  17. Grawenda A, O’Neill E (2015) Clinical utility of RASSF1A methylation in human malignancies. Br J Cancer 113:372–381CrossRefPubMedPubMedCentralGoogle Scholar
  18. Gumbiner B (2000) Regulation of cadherin adhesive activity. J Cell Biol 148:399–404CrossRefPubMedPubMedCentralGoogle Scholar
  19. Guo C, Tommasi S, Yee J et al (2007) RASSF1A is part of a complex similar to the Drosophila Hippo/Salvador/Lats tumor-suppressor network. Curr Biol 17:700–705CrossRefPubMedGoogle Scholar
  20. Hara E, Smith R, Parry D (1996) Regilation of p16CDKN2 expression and its implications for cell immortalization and senescence. Mol Cel Biol 16:859–867CrossRefGoogle Scholar
  21. Hardisson D (2003) Molecular pathogenesis of head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol 260:502–508CrossRefPubMedGoogle Scholar
  22. Hashimoto M, Niwa O, Nitta Y et al (1989) Unstable expression of E-cadherin adhesion molecules in metastatic ovarian tumor cells. Jpn Cancer Res 80:459–463CrossRefGoogle Scholar
  23. Hesson L, Cooper W, Latif F (2007) The role of RASSF1 methylation in cancer. Dis Markers 23:73–87CrossRefPubMedPubMedCentralGoogle Scholar
  24. Huang Y, Chen L, Guo L et al (2014) Evaluating DAPK as a therapeutic target. Apoptosis 19:371–386CrossRefPubMedGoogle Scholar
  25. Kamb A (1995) Cell-cycle regulators and cancer. Trends Genet 11:136–140CrossRefPubMedGoogle Scholar
  26. Khanal S, Joh J, Kwon A et al (2015) Human papillomavirus E7 serology and association with p16 immunohistochemistry in squamous cell carcinoma of the head and neck. Exp Mol Pathol 99:335–340CrossRefPubMedGoogle Scholar
  27. Khor G, Froemming G, Zain S et al (2013) DNA methylation profiling revealed promoter hypermethylation-induced silencing of p16, DDAH2 and DUSP I in primary oral squamous cell carcinoma. Int J Med Sci 10:1727–1739CrossRefPubMedPubMedCentralGoogle Scholar
  28. Kottorou AE, Antonacopoulou AG, Dimitrakopoulos FI et al (2012) Altered expression of NFY-C and RORA in colorectal adenocarcinomas. Acta Histochem 114:553–561CrossRefPubMedGoogle Scholar
  29. Kouketsu A, Sato I, Abe S et al (2015) Detection of human papillomavirus infection in oral squamous cell carcinoma: a cohort study of Japanese patients. J Oral Pathol Med. doi: 10.1111/jop.12416 PubMedGoogle Scholar
  30. Lee JM, Kim IS, Kim H et al (2010) RORalpha attenuates Wnt/beta-catenin signaling by PKCalpha-dependent phosphorylation in colon cancer. Mol Cell 37:183–195CrossRefPubMedGoogle Scholar
  31. Leemans CR, Braakhuis BJ, Brakenhoff RH (2011) The molecular biology of head and neck cancer. Nat Rev Cancer 11:9–22CrossRefPubMedGoogle Scholar
  32. Li J, Huang T, Zhang C et al (2015) Association between RASSF1A Promoter Hypermethylation and Oncogenic HPV Infection Status in Invasive Cervical Cancer: a Meta-analysis. Asian Pac J Cancer Prev 16:5749–5754CrossRefPubMedGoogle Scholar
  33. Lowry OH, Rosebrough NJ, Farr AL et al (1951) Protein measurements with the Folin Phenol Reagent. J BiolChem 193:267–275Google Scholar
  34. Majchrzak E, Szybiak B, Wegner A et al (2014) Oral cavity and oropharyngeal squamous cell carcinoma in young adults: a review of the literature. Radiol Oncol 48:1–10CrossRefPubMedPubMedCentralGoogle Scholar
  35. Martoriati A, Doumont G, Alcalay M et al (2005) dapk1, encoding an activator of a p19ARF-p53-mediated apoptotic checkpoint, is a transcription target of p53. Oncogene 24:1461–1466CrossRefPubMedGoogle Scholar
  36. Matsukura S, Miyazaki K, Yakushiji H et al (2001) Expression and prognostic significance of O6-methylguanine-DNA methyltransferase in hepatocellular, gastric, and breast cancers. Ann Surg Oncol 8:807–816CrossRefPubMedGoogle Scholar
  37. McDowell L, Young R, Johnston M et al (2016) p16-positive lymph node metastases from cutaneous head and neck squamous cell carcinoma: no association with high-risk human papillomavirus or prognosis and implications for the workup of the unknown primary. Cancer 122:1201–1208CrossRefPubMedGoogle Scholar
  38. Mino N, Takenaka K, Sonobe M et al (2007) Expression of tissue inhibitor of metalloproteinase-3 (TIMP-3) and its prognostic significance in resected non-small cell lung cancer. J Surg Oncol 95:250–257CrossRefPubMedGoogle Scholar
  39. Miyazaki T, Kato H, Nakjima M et al (2004) An immunohistochemical study of TIMP-3 expression in oesophageal squamous cell carcinoma. Br J Cancer 91:1556–1560PubMedPubMedCentralGoogle Scholar
  40. Nagathihalli N, Massion P, Gonzalez A et al (2012) Smoking induces epithelial-to-mesenchymal transition in non-small cell lung cancer through HDAC-mediated downregulation of E-cadherin. Mol Cancer Ther 11:2362–2372CrossRefPubMedPubMedCentralGoogle Scholar
  41. O’Hurley G, Perry AS, O’Grady A et al (2011) The role of secreted frizzled-related protein 2 expression in prostate cancer. Histopathology 59:1240–1248CrossRefPubMedGoogle Scholar
  42. Pannone G, Santoro A, Feola A et al (2014) The role of E-cadherin down-regulation in oral cancer: CDH1 gene expression and epigenetic blockage. Curr Cancer Drug Targets 14:115–127CrossRefPubMedGoogle Scholar
  43. Pastuszak-Lewandoska D, Kordiak J, Migdalska-Sek M et al (2015) Quantitative analysis of mRNA expression levels and DNA methylation profiles of three neighboring genes: FUS1, NPRL2/G21 and RASSF1A in non-small cell lung cancer patients. Respir Res 16:76CrossRefPubMedPubMedCentralGoogle Scholar
  44. Pérez-Sayáns García M, Suárez-Peñaranda JM, Gayoso-Diz P et al (2012) Tissue inhibitor of metalloproteinases in oral squamous cell carcinomas - a therapeutic target? Cancer Lett 323:11–19CrossRefPubMedGoogle Scholar
  45. Pérez-Sayáns M, Suárez-Peñaranda J, Herranz-Carnero M et al (2012) The role of the adenomatous polyposis coli (APC) in oral squamous cell carcinoma. Oral Oncol 48:56–60CrossRefPubMedGoogle Scholar
  46. Pietruszewska W, Kobos J, Gryczyński M et al (2008) Analysis of TIMP-1, TIMP-2 and TIMP-3 expression as a prognostic factor of laryngeal cancer progression. Otolaryngol Pol 62:380–387CrossRefPubMedGoogle Scholar
  47. Powell S, Zilz N, Beazer-Barclay Y et al (1992) APC mutations occur early during colorectal tumorigenesis. Nature 359:235–237CrossRefPubMedGoogle Scholar
  48. Puig-Butille J, Escámez M, Garcia-Garcia F et al (2013) Capturing the biological impact of CDKN2A and MC1R genes as an early predisposing event in melanoma and non melanoma skin cancer. Oncotarget 5:1439–1451PubMedCentralGoogle Scholar
  49. Qin Y, Ye GX, Wu CJ et al (2014) Effect of DAPK1 gene on proliferation, migration, and invasion of carcinoma of pancreas BxPC-3 cell line. Int J Clin Exp Pathol 7:7536–7544PubMedPubMedCentralGoogle Scholar
  50. Rampias T, Pectasides E, Prasad M et al (2013) Molecular profile of head and neck squamous cell carcinomas bearing p16 high phenotype. Ann Onc 24:2124–2131CrossRefGoogle Scholar
  51. Rayess H, Wang M, Srivatsan E (2012) Cellular senescence and tumor suppressor gene p16. Int J Cancer 130:1715–1725CrossRefPubMedGoogle Scholar
  52. Restucci B, Martano M, De Vico G et al (2009) Expression of E-Cadherin, β-catenin and APC protein in canine colorectal tumours. Antican Res 29:2919–2926Google Scholar
  53. Rodrigues PC, Miguel MC, Bagordakis E et al (2014) Clinicopathological prognostic factors of oral tongue squamous cell carcinoma: a retrospective study of 202 cases. Int J Oral Maxillofac Surg 43:795–801CrossRefPubMedGoogle Scholar
  54. Saito T, Mitomi H, Imamhasan A et al (2014) Downregulation of sFRP-2 by epigenetic silencing activates the β-catenin/Wnt signaling pathway in esophageal basaloid squamous cell carcinoma. Virchows Arch 464:135–143CrossRefPubMedGoogle Scholar
  55. Shah FD, Begum R, Vajaria BN et al (2011) A review on salivary genomics and proteomics biomarkers in oral cancer. Indian J Clin Biochem 26:326–334CrossRefPubMedPubMedCentralGoogle Scholar
  56. Theocharis S, Klijanienko J, Giaginis C et al (2011) Expression of DNA repair proteins, MSH2, MLH1 and MGMT in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients’ survival. J Oral Pathol Med 40:218–226CrossRefPubMedGoogle Scholar
  57. Tsuchiya R, Yamamoto G, Nagoshi Y et al (2004) Expression of adenomatous polyposis coli (APC) in tumorigenesis of human oral squamous cell carcinoma. Oral Oncol 40:932–940CrossRefPubMedGoogle Scholar
  58. Vizoso FJ, González LO, Corte MD et al (2007) Study of matrix metalloproteinases and their inhibitors in breast cancer. Br J Cancer 26:903–911CrossRefGoogle Scholar
  59. Wang X, Wu R, Hao T et al (2000) Effects of cigarette smoke extract on E-cadherin expression in cultured airway epithelial cells. J Tongii Med Univ 20:32–35CrossRefGoogle Scholar
  60. Wei DM, Liu DY, Lei DP et al (2015) Aberrant methylation and expression of DAPk1 in human hypopharyngeal squamous cell carcinoma. Acta Otolaryngol 135:70–78CrossRefPubMedGoogle Scholar
  61. Weyden L, Tachibana K, Gonzalez M et al (2005) The RASSF1A isoform of RASSF1 promotes microtubule stability and suppress tumorigenesis. Mol Cel Biol 25:8356–8367CrossRefGoogle Scholar
  62. Zeng C, Guo B, Chen J et al (2015) Expression profile of tumor suppressor gene RASSF1 in lacrimal gland carcinoma. Genet Mol Res 14:6993–6998CrossRefPubMedGoogle Scholar
  63. Zhu Y, McAvoy S, Kuhn R et al (2006) RORA, a large common fragile site gene, is involved in cellular stress response. Oncogene 25:2901–2908CrossRefPubMedGoogle Scholar
  64. Zuo C, Ai L, Ratliff P et al (2004) O6-methylguanine-DNA methyltransferase gene: epigenetic silencing and prognostic value in head and neck squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 13:967–975PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Joanna Katarzyna Strzelczyk
    • 1
    Email author
  • Karolina Gołąbek
    • 1
  • Piotr Cuber
    • 1
  • Łukasz Krakowczyk
    • 2
  • Aleksander Jerzy Owczarek
    • 3
  • Martyna Fronczek
    • 1
  • Piotr Choręża
    • 3
  • Edyta Hudziec
    • 4
  • Zofia Ostrowska
    • 1
  1. 1.Department of Medical and Molecular Biology, School of Medicine with the Division of Dentistry in ZabrzeMedical University of Silesia in KatowiceZabrzePoland
  2. 2.Clinic of Oncological and Reconstructive SurgeryMaria Sklodowska–Curie Memorial Cancer Center and Institute of OncologyGliwicePoland
  3. 3.Department of Statistics, Department of Instrumental Analysis, School of Pharmacy with the Division of Laboratory Medicine in SosnowiecMedical University of Silesia in KatowiceSosnowiecPoland
  4. 4.Department of Biochemistry, School of Medicine with the Division of Dentistry in ZabrzeMedical University of Silesia in KatowiceZabrzePoland

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