Tumor Biology

, Volume 36, Issue 12, pp 9717–9722 | Cite as

Association between cell cycle gene transcription and tumor size in oral squamous cell carcinoma

  • Marina Gonçalves Diniz
  • Jeane de Fatima Correia Silva
  • Fabricio Tinôco Alvim de Souza
  • Núbia Braga Pereira
  • Carolina Cavaliéri Gomes
  • Ricardo Santiago Gomez
Research Article

Abstract

Higher tumor size correlates with poor prognosis and is an independent predictive survival factor in oral squamous cell carcinoma (OSCC) patients. However, the molecular events underlining OSCC tumor evolution are poorly understood. We aimed to investigate if large OSCC tumors show different cell cycle gene transcriptional signature compared to small tumors. Seventeen fresh OSCC tumor samples with different tumor sizes (T) were included in the study. Tumors were from the tongue or from the floor of the mouth, and only three patients were nonsmokers. Samples were categorized according to clinical tumor size in tumors ≤2 cm (T1, n = 5) or tumors >2 cm (T2, n = 9; T3, n = 2; T4, n = 1). The group of tumors ≤2 cm was considered the reference group, while the larger tumors were considered the test group. We assessed the expression of 84 cell cycle genes by qRT-PCR array and normalized it to the expression of two housekeeping genes. Results were analyzed according to the formula 2^−DeltaCt. A five-fold change cutoff was used, and p values <0.05 were considered statistically significant. Ki-67 immunohistochemistry was performed to estimate cell proliferation index. Twenty-nine genes were downregulated in the test group (larger tumors) compared to the reference group (smaller tumors). Among these genes, 13 reached statistical significance: ANAPC4, CUL1, SUMO1, KPNA2, MAD2L2, CCNG2, E2F4, NBN, CUL2, PCNA, TFDP1, KNTC1, and ATR. Ki-67 labeling index was similar in both tumor groups. Our findings suggest that the transcriptional activity of specific cell cycle genes varies according to the size of OSCC tumor, which probably reflects tumor molecular evolution and adaptation to the microenvironment.

Keywords

Oral cancer Gene expression profiling Tumor grade Head and neck cancer Molecular alteration qPCR array 

Notes

Acknowledgments

This study was supported in part by the following Brazilian funding agencies: Coordination for the Improvement of Higher Education Personnel (CAPES), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), and National Council for Scientific and Technological Development (CNPq), Brazil. Diniz, M.G. is a research fellow at CAPES. Gomez, R.S. and Gomes, C.C. are research fellows at CNPq.

Conflict of interest

None.

References

  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015. doi: 10.1002/ijc.29210.PubMedCentralGoogle Scholar
  2. 2.
    Patel SG, Shah JP. TNM staging of cancers of the head and neck: striving for uniformity among diversity. Cancer J Clin. 2005. doi: 10.3322/canjclin.55.4.242.Google Scholar
  3. 3.
    Hanahan D, Weinberg RA. Hallmarks of cancer. Cell. 2011. doi: 10.1016/j.cell.2011.02.013.PubMedGoogle Scholar
  4. 4.
    Todd R, Hinds PW, Munger K, et al. Cell cycle dysregulation in oral cancer. Crit Rev Oral Biol Med. 2002. doi: 10.1177/154411130201300106.PubMedGoogle Scholar
  5. 5.
    Stewart BW, Wild CP, editors. World Cancer Report. 3rd ed. Lyon: IARC; 2014.Google Scholar
  6. 6.
    Helliwell T, Woolgar J. Dataset for histopathology reporting of mucosal malignancies of the oral cavity. London: The Royal College of Pathologists; 2013.Google Scholar
  7. 7.
    Kademani D, Bell RB, Bagheri S, et al. Prognostic factors in intra oral squamous cell carcinoma: the influence of histologic grade. J Oral Maxillofac Surg. 2005. doi: 10.1016/j.joms.2005.07.011.Google Scholar
  8. 8.
    Arduino PG, Carrozzo M, Chiecchio A, et al. Clinical and histopathologic independent prognostic factors in oral squamous cell carcinoma: a retrospective study of 334 cases. J Oral Maxillofac Surg. 2008. doi: 10.1016/j.joms.2007.12.024.PubMedGoogle Scholar
  9. 9.
    Sobin L, Gospodarowicz M, Wittekind C, editors. TNM Classification of Malignant Tumours. 8th ed. New Jersey: Wiley; 2009.Google Scholar
  10. 10.
    Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010. doi: 10.1016/S1470-2045(09)70311-0.PubMedGoogle Scholar
  11. 11.
    Warnakulasuriya S. Prognostic and predictive markers for oral squamous cell carcinoma: the importance of clinical, pathological and molecular markers. Saudi J Med Med Sci. 2014. doi: 10.4103/1658-631X.128400.Google Scholar
  12. 12.
    Tabatabaeifar S, Kruse TA, Thomassen M, et al. Use of next generation sequencing in head and neck squamous cell carcinomas: a review. Oral Oncol. 2014. doi: 10.1016/j.oraloncology.2014.08.013.PubMedGoogle Scholar
  13. 13.
    Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer. 2011. doi: 10.1038/nrc2981.PubMedGoogle Scholar
  14. 14.
    Jones RG, Thompson CB. Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes Dev. 2009. doi: 10.1101/gad.1756509.Google Scholar
  15. 15.
    Sullivan GM, Feinn R. Using effect size-or why the p value is not enough. J Grad Med Educ. 2012. doi: 10.4300/JGME-D-12-00156.1.Google Scholar
  16. 16.
    The human protein atlas, http://www.proteinatlas.org
  17. 17.
    Uhlen M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, et al. Tissue-based map of the human proteome. Science. 2015. doi: 10.1126/science.1260419.PubMedGoogle Scholar
  18. 18.
    Sun Y. Targeting E3 ubiquitin ligases for cancer therapy. Cancer Biol Ther. 2003. doi: 10.4161/cbt.2.6.677.Google Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Marina Gonçalves Diniz
    • 1
  • Jeane de Fatima Correia Silva
    • 1
  • Fabricio Tinôco Alvim de Souza
    • 1
  • Núbia Braga Pereira
    • 1
  • Carolina Cavaliéri Gomes
    • 2
  • Ricardo Santiago Gomez
    • 1
  1. 1.Department of Oral Surgery and Pathology, School of DentistryUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  2. 2.Department of Pathology, Biological Sciences InstituteUniversidade Federal de Minas GeraisBelo HorizonteBrazil

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