Quantitative determination of c-myc facilitates the assessment of prognosis of OSCC patients

Pérez-Sayáns,M.; Suárez-Peñaranda,J. M.; Padín-Iruegas,E.; Gayoso-Diz,P.; Reis-De Almeida,M.; Barros-Angueira,F.; Gándara-Vila,P.; Blanco-Carrión,A.; García-García,A.

doi:10.3892/or.2014.3040

Quantitative determination of c-myc facilitates the assessment of prognosis of OSCC patients

Authors:
- M. Pérez-Sayáns
- J. M. Suárez-Peñaranda
- E. Padín-Iruegas
- P. Gayoso-Diz
- M. Reis-De Almeida
- F. Barros-Angueira
- P. Gándara-Vila
- A. Blanco-Carrión
- A. García-García
View Affiliations

Affiliations: Oral Medicine, Oral Surgery and Implantology Unit, Faculty of Medicine and Dentistry, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain, Department of Pathology and Forensic Sciences, University Hospital and School of Medicine of Santiago de Compostela, Santiago de Compostela, Spain, Laboratorio Oncología Traslacional, Fundación Idichus, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain, Clinical Epidemiology and Biostatistics Unit, Hospital Clínico Universitario de Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain, Unidad de Medicina Molecular, Fundación Pública Galega de Medicina Xenómica, Edificio de Consultas Planta-2, Hospital Clinico Universitario, Santiago de Compostela, Spain
Published online on: February 20, 2014 https://doi.org/10.3892/or.2014.3040
Pages: 1677-1682

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Myc genes are a family of proto-oncogenes whose proteins are implicated in the regulation of cell proliferation, differentiation and apoptosis, and in regulating the activity of genes involved in cell division. The aim of the present study was to establish a quantitative description of the expression of c-myc and evaluate its relationship with other clinical and prognostic factors, as well as to establish a multivariate survival prediction model. This is a retrospective study of 68 patients diagnosed with oral squamous cell carcinoma (OSCC). We constructed a tissue microarray for investigating the expression of c-myc by immunohistochemistry. Statistical analyses were carried out, and a multivariate model that predicts survival was established. The average expression of c-myc was 50.32 (SD, 26.05) with a range from 6.60 to 99.48; similar for initial and advanced tumor stages. Non-smoking patients had higher levels of c-myc, showing statistically significant differences (Kruskal-Wallis χ2=5.975; p=0.05). We found no statistically significant relationship between the quantitative expression of c-myc and any other clinical or pathological parameters. For each unit of increase of c-myc, the risk increased by 1.15 (p<0.001; HR, 1.150; 95% CI, 1062-1245). Further study of this protein, which may have a significant diagnostic, prognostic and therapeutic value is warranted. Its determination can be valuable when used together with other markers to assess the prognosis of OSCC patients.

View Figures

View References

1	Perez-Sayans M, Somoza-Martin JM, Barros-Angueira F, Reboiras-Lopez MD, Gandara Rey JM and Garcia-Garcia A: Genetic and molecular alterations associated with oral squamous cell cancer (Review). Oncol Rep. 22:1277–1282. 2009. View Article : Google Scholar : PubMed/NCBI
2	Choi S and Myers JN: Molecular pathogenesis of oral squamous cell carcinoma: implications for therapy. J Dent Res. 87:14–32. 2008. View Article : Google Scholar : PubMed/NCBI
3	Vairaktaris E, Spyridonidou S, Papakosta V, et al: The hamster model of sequential oral oncogenesis. Oral Oncol. 44:315–324. 2008. View Article : Google Scholar : PubMed/NCBI
4	Ginos MA, Page GP, Michalowicz BS, et al: Identification of a gene expression signature associated with recurrent disease in squamous cell carcinoma of the head and neck. Cancer Res. 64:55–63. 2004. View Article : Google Scholar : PubMed/NCBI
5	Perez-Sayans M, Pilar GD, Barros-Angueira F, Suarez-Penaranda JM, et al: Current trends in miRNAs and their relationship with oral squamous cell carcinoma. J Oral Pathol Med. 41:433–443. 2012. View Article : Google Scholar : PubMed/NCBI
6	Shah NG, Trivedi TI, Tankshali RA, et al: Prognostic significance of molecular markers in oral squamous cell carcinoma: a multivariate analysis. Head Neck. 31:1544–1556. 2009. View Article : Google Scholar : PubMed/NCBI
7	Gallant P and Steiger D: Myc’s secret life without Max. Cell Cycle. 8:3848–3853. 2009.
8	Pelengaris S, Khan M and Evan G: c-MYC: more than just a matter of life and death. Nat Rev Cancer. 2:764–776. 2002. View Article : Google Scholar : PubMed/NCBI
9	Whyte DA, Broton CE and Shillitoe EJ: The unexplained survival of cells in oral cancer: what is the role of p53? J Oral Pathol Med. 31:125–133. 2002. View Article : Google Scholar : PubMed/NCBI
10	Lebofsky R and Walter JC: New Myc-anisms for DNA replication and tumorigenesis? Cancer Cell. 12:102–103. 2007.
11	Spandidos DA, Yiagnisis M, Papadimitriou K and Field JK: ras, c-myc and c-erbB-2 oncoproteins in human breast cancer. Anticancer Res. 9:1385–1393. 1989.PubMed/NCBI
12	Varley JM, Swallow JE, Brammar WJ, Whittaker JL and Walker RA: Alterations to either c-erbB-2(neu) or c-myc proto-oncogenes in breast carcinomas correlate with poor short-term prognosis. Oncogene. 1:423–430. 1987.PubMed/NCBI
13	Riou GF: Proto-oncogenes and prognosis in early carcinoma of the uterine cervix. Cancer Surv. 7:441–456. 1988.PubMed/NCBI
14	Field JK, Spandidos DA, Stell PM, Vaughan ED, Evan GI and Moore JP: Elevated expression of the c-myc oncoprotein correlates with poor prognosis in head and neck squamous cell carcinoma. Oncogene. 4:1463–1468. 1989.PubMed/NCBI
15	Nakagawa M, Takizawa N, Narita M, Ichisaka T and Yamanaka S: Promotion of direct reprogramming by transformation-deficient Myc. Proc Natl Acad Sci USA. 107:14152–14157. 2010. View Article : Google Scholar : PubMed/NCBI
16	Adams JM, Kelly PN, Dakic A, Carotta S, Nutt SL and Strasser A: Role of ‘cancer stem cells’ and cell survival in tumor development and maintenance. Cold Spring Harb Symp Quant Biol. 73:451–459. 2008.
17	Eilers M and Eisenman RN: Myc’s broad reach. Genes Dev. 22:2755–2766. 2008.
18	Nair SK and Burley SK: Structural aspects of interactions within the Myc/Max/Mad network. Curr Top Microbiol Immunol. 302:123–143. 2006.PubMed/NCBI
19	American Joint Committee on Cancer. Lip and oral cavity. Cancer Staging Manual. Edge SB, Fritz AG, Byrd DR, Greene FL, Trotti A III and Compton CC: 7th edition. Springer; New York: pp. 1–4. 2010
20	Kononen J, Bubendorf L, Kallioniemi A, et al: Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med. 4:844–847. 1998. View Article : Google Scholar : PubMed/NCBI
21	World Health Organization Classification of Tumours. Head and Neck Tumors. Pathology and Genetics. Barnes L, Eveson JW, Reichart P and Sidransky D: 9 edition. IARC Press; Lyon: pp. 177–180. 2005
22	Heagerty PJ, Lumley T and Pepe MS: Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics. 56:337–344. 2000. View Article : Google Scholar : PubMed/NCBI
23	Goessel G, Quante M, Hahn WC, et al: Creating oral squamous cancer cells: a cellular model of oral-esophageal carcinogenesis. Proc Natl Acad Sci USA. 102:15599–15604. 2005. View Article : Google Scholar : PubMed/NCBI
24	Foster KW, Ren S, Louro ID, et al: Oncogene expression cloning by retroviral transduction of adenovirus E1A-immortalized rat kidney RK3E cells: transformation of a host with epithelial features by c-MYC and the zinc finger protein GKLF. Cell Growth Differ. 10:423–434. 1999.
25	Perez-Sayans M, Suarez-Penaranda JM, Pilar GD, Barros-Angueira F, Gandara-Rey JM and Garcia-Garcia A: What real influence does the proto-oncogene c-myc have in OSCC behavior? Oral Oncol. 47:688–692. 2011. View Article : Google Scholar : PubMed/NCBI
26	Freier K, Bosch FX, Flechtenmacher C, et al: Distinct site-specific oncoprotein overexpression in head and neck squamous cell carcinoma: a tissue microarray analysis. Anticancer Res. 23:3971–3977. 2003.PubMed/NCBI
27	Baral R, Patnaik S and Das BR: Co-overexpression of p53 and c-myc proteins linked with advanced stages of betel- and tobacco-related oral squamous cell carcinomas from eastern India. Eur J Oral Sci. 106:907–913. 1998. View Article : Google Scholar : PubMed/NCBI
28	Vora HH, Shah NG, Patel DD, Trivedi TI and Chikhlikar PR: Prognostic significance of biomarkers in squamous cell carcinoma of the tongue: multivariate analysis. J Surg Oncol. 82:34–50. 2003. View Article : Google Scholar : PubMed/NCBI
29	Takes RP, Baatenburg de Jong RJ, Schuuring E, Litvinov SV, Hermans J and Van Krieken JH: Differences in expression of oncogenes and tumor suppressor genes in different sites of head and neck squamous cell. Anticancer Res. 18:4793–4800. 1998.PubMed/NCBI
30	Shah NG, Trivedi TI, Tankshali RA, et al: Molecular alterations in oral carcinogenesis: significant risk predictors in malignant transformation and tumor progression. Int J Biol Markers. 22:132–143. 2007.PubMed/NCBI
31	Martin-Ezquerra G, Salgado R, Toll A, et al: Multiple genetic copy number alterations in oral squamous cell carcinoma: study of MYC, TP53, CCDN1, EGFR and ERBB2 status in primary and metastatic tumours. Br J Dermatol. 163:1028–1035. 2010. View Article : Google Scholar : PubMed/NCBI
32	Fujieda S, Inuzuka M, Tanaka N, et al: Expression of p27 is associated with Bax expression and spontaneous apoptosis in oral and oropharyngeal carcinoma. Int J Cancer. 84:315–320. 1999. View Article : Google Scholar : PubMed/NCBI
33	Hayry V, Makinen LK, Atula T, et al: Bmi-1 expression predicts prognosis in squamous cell carcinoma of the tongue. Br J Cancer. 102:892–897. 2010. View Article : Google Scholar : PubMed/NCBI
34	Takes RP, Baatenburg de Jong RJ, Wijffels K, et al: Expression of genetic markers in lymph node metastases compared with their primary tumours in head and neck cancer. J Pathol. 194:298–302. 2001. View Article : Google Scholar : PubMed/NCBI
35	Rodrigo JP, Lazo PS, Ramos S, Alvarez I and Suarez C: MYC amplification in squamous cell carcinomas of the head and neck. Arch Otolaryngol Head Neck Surg. 122:504–507. 1996. View Article : Google Scholar : PubMed/NCBI
36	Eversole LR and Sapp JP: c-myc oncoprotein expression in oral precancerous and early cancerous lesions. Eur J Cancer B Oral Oncol. 29B:131–135. 1993. View Article : Google Scholar : PubMed/NCBI
37	Tsuzuki H, Sunaga H, Ito T, Narita N, Sugimoto C and Fujieda S: Reliability of platelet-derived endothelial cell growth factor as a prognostic factor for oral and oropharyngeal carcinomas. Arch Otolaryngol Head Neck Surg. 131:1071–1078. 2005. View Article : Google Scholar : PubMed/NCBI