Skip to main content

Advertisement

Log in

A Review on Salivary Genomics and Proteomics Biomarkers in Oral Cancer

  • Review Article
  • Published:
Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

Oral cancer has emerged as an alarming public health problem with increasing incidence and mortality rates all over the world. Therefore, the implementation of newer screening and early detection approaches are of utmost importance which could reduce the morbidity and mortality associated with this disease. Sensitive and specific biomarkers for oral cancer are likely to be most effective for screening, diagnosis, staging and follow-up for this dreaded malignancy. Unlike other deep cancers, oral cancer is located in oral cavity. Hence, the direct contact between saliva and oral cancer lesion makes the measurement of tumor markers in saliva an attractive alternative to serum and tissue testing. The DNA, RNA and protein molecules derived from the living cancer cells can be conveniently obtained from saliva. Thus, salivary biomarkers, a non-invasive alternative to serum and tissue-based biomarkers may be an effective modality for early diagnosis, prognostication and monitoring post therapy status. In the current post-genomic era, various technologies provide opportunities for high-throughput approaches to genomics and proteomics; which have been used to evaluate altered expressions of gene and protein targets in saliva of oral cancer patients. The emerging field of salivary biomarkers has great potentials to prove its clinical significance to combat oral cancer. Hence, we have reviewed importance of several salivary genomics and proteomics biomarkers for oral cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.

    Article  CAS  PubMed  Google Scholar 

  2. Subramanian S, Sankaranarayanan R, Bapat B, Somanathan T, Thomas G, Mathew B, et al. Cost-effectiveness of oral cancer screening: results from a cluster randomized controlled trial in India. Bull World Health Organ. 2009;87:200–6.

    Article  PubMed  Google Scholar 

  3. Misra C, Majumder M, Bajaj S, Ghosh S, Roy B, Roychoudhury S. Polymorphism at p53, p73, and MDM2 loci modulate the risk of tobacco associated leukoplakia and oral cancer. Mol Carcinog. 2009;48:790–800.

    Article  CAS  PubMed  Google Scholar 

  4. Boyle P, Levin B, editors. World cancer report 2008. Lyon: International Agency for Research on Cancer; 2008. 330 pp.

  5. Patel JB, Shah FD, Shukla SN, Shah PM, Patel PM. Role of nitric oxide and antioxidant enzymes in the pathogenesis of oral cancer. J Cancer Res Ther. 2009;5:247–53.

    Article  CAS  PubMed  Google Scholar 

  6. Slaughter DL, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium: clinical implication of multicentric origins. Cancer. 1953;6:963–8.

    Article  CAS  PubMed  Google Scholar 

  7. Mishra M, Mohanty J, Sengupta S, Tripathy S. Epidemiological and clinicopathological study of oral lekoplakia. Indian J Dermatol Venereol Leprol. 2005;71:161–5.

    Article  PubMed  Google Scholar 

  8. Wu JY, Yi C, Chung HR, Wang DJ, Chang WC, Lee SY, et al. Potential biomarkers in saliva for oral squamous cell carcinoma. Oral Oncol. 2010;46:226–31.

    Article  CAS  PubMed  Google Scholar 

  9. Pink R, Simek J, Vondrakova J, Faber E, Michl P, Pazdera J, et al. Saliva as a diagnostic medium. Biomed Pap Med Fac Univ Palacky Olocouc Czech Repub. 2009;153:103–10.

    CAS  Google Scholar 

  10. Messadi DV, Wilder SP, Wolinsky L. Improving oral cancer survival: the role of dental providers. J Calif Dent Assoc. 2009;37:789–98.

    PubMed  Google Scholar 

  11. Wong DT. Towards a simple, saliva-based test for the detection of oral cancer. ‘oral fluid (saliva), which is the mirror of the body, is a perfect medium to be explored for health and disease surveillance’. Expert Rev Mol Diagn. 2006;6:267–72.

    Article  PubMed  Google Scholar 

  12. Leston JS, Dios PD. Diagnostic clinical aids in oral cancer. Oral Oncol. 2010;46:418–22.

    Article  Google Scholar 

  13. Shiptzer T, Hamzany Y, Bahar G, Feinmesser R, Savulescu D, Borovoi I, et al. Salivary analysis of oral cancer biomarkers. Br J Cancer. 2009;101:1194–8.

    Article  Google Scholar 

  14. Cassolato SF, Turnbull RS. Xerostomia: clinical aspects and treatment. Gerodontology. 2003;20:64–77.

    Article  PubMed  Google Scholar 

  15. Brosky ME. The role of saliva in oral health: strategies for prevention and management of xerostomia. J Support Oncol. 2007;5:215–25.

    CAS  PubMed  Google Scholar 

  16. Ahmadi Motamayel F, Davoodi P, Dalband M, Hendi SS. Saliva as a mirror of the body health. DJH. 2010;2:1–15.

    Google Scholar 

  17. Zimmermann BG, Park NJ, Wong DT. Genomic targets in saliva. Ann NY Acad Sci. 2007;1098:184–91.

    Article  CAS  PubMed  Google Scholar 

  18. Jiang J, Park NJ, Hu S, Wong DT. A universal pre-analytic for concurrent stabilization of salivary proteins, RNA and DNA at ambient temperature. Arch Oral Biol. 2009;54:268–73.

    Article  CAS  PubMed  Google Scholar 

  19. Wong DT. Salivary diagnostics powered by nanotechnologies, proteomics and genomics. J Am Dent Assoc. 2006;137:313–21.

    CAS  PubMed  Google Scholar 

  20. Streckfus CF, Dubinsky WP. Proteomic analysis of saliva for cancer diagnosis. Expert Rev Proteomics. 2007;4:329–32.

    Article  CAS  PubMed  Google Scholar 

  21. Streckfus CF, Bigler L, Tucci M, Thigpen JT. A preliminary study of CA l5-3, c-erbB-2, EGFR, cathepsin-D and p53 in saliva among women with breast carcinoma. Cancer Investig. 2000;18:101–19.

    Article  CAS  Google Scholar 

  22. Chen DX, Schwartz PE, Li FQ. Salivary and serum CA 125 assays for detecting malignant ovarian tumors. Obstet Gynecol. 1990;75:701–14.

    CAS  PubMed  Google Scholar 

  23. Schapher M, Wendler O, Groschl M, Schafer R, Iro H, Zenk J. Salivary leptin as a candidate diagnostic marker in salivary gland tumors. Clin Chem. 2009;55:914–22.

    Article  CAS  PubMed  Google Scholar 

  24. Wu ZZ, Wang JG, Zhang XL. Diagnostic model of saliva protein finger print analysis of patients with gastric cancer. World J Gastroenterol. 2009;15:865–70.

    Article  CAS  PubMed  Google Scholar 

  25. Wong DT, Zhang L, Farrell J, Zhou F, Elashoff D, Gao K, et al. Salivary biomarkers for pancreatic cancer detection [abstract]. J Clin Oncol. 2009;27(Suppl 15S):4630.

    Google Scholar 

  26. Nagler RM. Saliva as a tool for oral cancer diagnosis and prognosis. Oral Oncol. 2009;45:1006–16.

    Article  CAS  PubMed  Google Scholar 

  27. Rhodus NL, Ho V, Miller CS, Myers S, Ondrey F. NF-kB dependent cytokines levels in saliva of patients with oral preneoplastic lesions and oral squamous cell carcinoma. Cancer Detect Prev. 2005;29:42–5.

    Article  CAS  PubMed  Google Scholar 

  28. St John MA, Li Y, Zhou X, Denny P, Ho CM, Montemagno C, et al. Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 2004;130:929–35.

    Article  PubMed  Google Scholar 

  29. Dowling P, Wormald R, Meleady P, Henry M, Curran A, Clynes M. Analysis of the saliva proteome from patients with head and neck squamous cell carcinoma reveals differences in abundance levels of proteins associated with tumor progression and metastasis. J Proteomics. 2008;71:168–75.

    Article  CAS  PubMed  Google Scholar 

  30. Zhong LP, Chen GF, Xu ZF, Zhang X, Ping FY, Zhao SF. Detection of telomerase activity saliva from oral squamous cell carcinoma patients. Int J Oral Maxillofac Surg. 2005;34:566–70.

    Article  PubMed  Google Scholar 

  31. Franzmann EJ, Reategui EP, Carraway KL, Hamilton KL, Weed DT, Goodwin WJ. Salivary soluble CD44: a potential molecular marker for head and neck cancer. Cancer Epidemiol Biomark Prev. 2005;14:735–9.

    Article  CAS  Google Scholar 

  32. Liao PH, Chang YC, Huang MF, Tai KW, Chou MY. Mutation of p53 gene codon 63 in saliva as a molecular marker for oral squamous cell carcinoma. Oral Oncol. 2000;36:272–6.

    Article  PubMed  Google Scholar 

  33. Warnakulasuriya S, Soussi T, Maher R, Johnson N, Tavassoli M. Expression of p53 in oral squamous cell carcinoma is associated with the presence of IgG and IgA p53 in sera and saliva of the patients. J Pathol. 2000;192:52–7.

    Article  CAS  PubMed  Google Scholar 

  34. Sainger RN, Shah MH, Desai AA, Shukla SN, Shah PM, Telang SD, et al. Clinical significance of serum p53 antibodies in oral cancer. Tumori. 2006;92:134–9.

    CAS  PubMed  Google Scholar 

  35. Yamazaki Y, Chiba I, Ishikawa M, Satoh C, Notani K, Ohiro Y, et al. Serum p53 antibodies as a prognostic indicator in oral squamous cell carcinoma. Odontology. 2008;96:32–7.

    Article  CAS  PubMed  Google Scholar 

  36. El-Naggar AK, Mao L, Staerkel G, Coombes MM, Tucker SL, Luna MA, et al. Genetic heterogeneity in saliva from patients with oral squamous carcinomas: implications in molecular diagnosis and screening. J Mol Diagn. 2001;3:164–70.

    Article  CAS  PubMed  Google Scholar 

  37. Bahar G, Feinmesser R, Shpitzer T, Popovtzer A, Nagler RM. Salivary analysis in oral cancer patients: DNA and protein oxidation, reactive nitrogen species, and antioxidant profile. Cancer. 2007;109:54–9.

    Article  CAS  PubMed  Google Scholar 

  38. Sato J, Goto J, Murata T, Kitamori S, Yamazaki Y, Satoh A, et al. Changes in saliva interleukin-6 levels in patients with oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;110:330–6.

    Article  PubMed  Google Scholar 

  39. Brailo V, Vacicevic-Boras V, Cekic-Arambasin A, Alajbeg IZ, Milenovic A, Lukac J. The significance of salivary interleukin 6 and tumor necrosis factor alpha in patients with oral leukoplakia. Oral Oncol. 2006;42:370–3.

    Article  CAS  PubMed  Google Scholar 

  40. Duffy SA, Taylor JM, Terrell JE, Islam M, Li Y, Fowler KE, et al. Interleukin-6 predicts recurrence and survival among head and neck cancer patients. Cancer. 2008;113:750–7.

    Article  PubMed  Google Scholar 

  41. Zhao M, Rosemenbaum E, Carvalho AL, Koch W, Jiang WW, Sidransky D, et al. Feasibility of quantitative PCR-based saliva rinse screening of HPV for head and neck cancer. Int J Cancer. 2005;117:605–10.

    Article  CAS  PubMed  Google Scholar 

  42. Hu S, Arellano M, Boontheung P, Wang J, Zhou H, Jiang J, et al. Salivary proteomics for oral cancer biomarker discovery. Clin Cancer Res. 2008;14:6246–52.

    Article  CAS  PubMed  Google Scholar 

  43. de Jong EP, Xie H, Onsongo G, Stone MD, Chen XB, Kooren JA, et al. Quantitative proteomics Revels myosin, actin as promising saliva biomarkers for distinguishing pre-malignant, malignant oral lesions. PLoS One. 2010;5:e11148.

    Article  PubMed  Google Scholar 

  44. Jou YJ, Lin CD, Lai CH, Chen CH, Kao JY, Chen SY, et al. Proteomic identification of salivary transferrin as a biomarker for early detection of oral cancer. Anal Chim Acta. 2010;681:41–8.

    Article  CAS  PubMed  Google Scholar 

  45. Zimmermann BG, Wong DT. Salivary mRNA targets for cancer diagnostics. Oral Oncol. 2008;44:425–9.

    Article  CAS  PubMed  Google Scholar 

  46. Viet CT, Schmidt BL. Methylation array analysis of preoperative and postoperative saliva DNA in oral cancer patients. Cancer Epidemiol Biomark Prev. 2008;17:3603–11.

    Article  CAS  Google Scholar 

  47. Nakahara Y, Shintani S, Mihara M, Hino S, Hamakawa H. Detection of p16 promoter methylation in serum of oral cancer patients. Int J Oral Maxillofac Surg. 2006;35:362–5.

    Article  CAS  PubMed  Google Scholar 

  48. Viet CT, Jordan RC, Schmidt BL. DNA promoter hypermethylation in saliva for the early diagnosis of oral cancer. J Calif Dent Assoc. 2007;35:844–9.

    CAS  PubMed  Google Scholar 

  49. Wei F, Patel P, Liao W, Chaudhry K, Zhang L, Garcia MA, et al. Electrochemical sensor for multiplex biomarkers detection. Clin Cancer Res. 2009;15:4446–52.

    Article  CAS  PubMed  Google Scholar 

  50. Brinkmann O, Kastratovic DA, Dimitrijevic MV, Konstantinovic VS, Jelovac DB, Antic J, et al. Oral squamous cell carcinoma detection by salivary biomarkers in a Serbian population. Oral Oncol. 2011;47:51–5.

    Article  CAS  PubMed  Google Scholar 

  51. Vairaktaris E, Yapijakis C, Serefoglou Z, Avgoustidis D, Critselis E, Spyridonidou S, et al. Gene expression polymorphisms of interleukins-1 beta, -4, -6, -8, -10, and tumor necrosis factors-alpha, -beta: regression analysis of their effect upon oral squamous cell carcinoma. J Cancer Res Clin Oncol. 2008;134:821–32.

    Article  CAS  PubMed  Google Scholar 

  52. Yapijakis C, Vairaktaris E, Vassiliou S, Vylliotis A, Nkenke E, Nixon AM, et al. The low VEGF production allele of the +936C/T polymorphism is strongly associated with increased risk for oral cancer. J Cancer Res Clin Oncol. 2007;133:787–91.

    Article  CAS  PubMed  Google Scholar 

  53. Sabitha K, Reddy MV, Jamil K. Smoking related risk involved in individuals carrying genetic variants of CYP1A1 gene in head and neck cancer. Cancer Epidemiol. 2010;34:587–92.

    Article  CAS  PubMed  Google Scholar 

  54. Gatoo MA, Siddiqui M, Farhan AK, Kozgar MI, Owais M. Oral cancer and gene polymorphisms: international status with special reference to India. Asian J Biochem. 2011;6:113–21.

    Article  CAS  Google Scholar 

  55. Anantharaman D, Chaubal PM, Kannan S, Bhisey RA, Mahimkar MB. Susceptibility to oral cancer by genetic polymorphisms at CYP1A1, GSTM1 and GSTT1 loci among Indians: tobacco exposure as a risk modulator. Carcinogenesis. 2007;28:1455–62.

    Article  CAS  PubMed  Google Scholar 

  56. Sainger RN, Shah FD, Telang SD, Shah PM, Patel PS. Telomere attrition and telomerase activity are associated with GSTM1 polymorphism in oral cancer. Cancer Biomark. 2009;5:189–95.

    CAS  PubMed  Google Scholar 

  57. Patel BP, Shah PM, Rawal UM, Desai AA, Shah SV, Rawal RM, et al. Activation of MMP-2 and MMP-9 in patients with oral squamous cell carcinoma. J Surg Oncol. 2005;90:81–8.

    Article  CAS  PubMed  Google Scholar 

  58. Patel BP, Shah SV, Shukla SN, Shah PM, Patel PS. Clinical significance of MMP-2 and MMP-9 in patients with oral cancer. Head Neck. 2007;29:564–72.

    Article  PubMed  Google Scholar 

  59. Singh RD, Haridas N, Patel JB, Shah FD, Shukla SN, Shah PM, et al. Matrix metalloproteinases and their inhibitors: correlation with invasion and metastasis in oral cancer. Ind J Clin Biochem. 2010;25:250–9.

    Article  CAS  Google Scholar 

  60. Patel PS, Raval GN, Rawal RM, Patel MM, Balar DB, Patel DD. Importance of glycoproteins in human cancer. Indian J Biochem Biophys. 1997;34:226–33.

    CAS  PubMed  Google Scholar 

  61. Raval GN, Patel DD, Parekh LJ, Patel JB, Shah MH, Patel PS. Evaluation of serum sialic acid, sialyltransferase and sialoproteins in oral cavity cancer. Oral Dis. 2003;9:119–28.

    Article  CAS  PubMed  Google Scholar 

  62. Rajpura KB, Patel PS, Chawda JG, Shah RM. Clinical significance of total and lipid bound sialic acid levels in oral-precancerous conditions and oral cancer. J Oral Pathol Med. 2005;34:263–7.

    Article  CAS  PubMed  Google Scholar 

  63. Shah MH, Telang SD, Shah PM, Patel PS. Tissue and serum α2-3- and α2-6-linkage specific sialylation changes in oral carcinogenesis. Glycoconjug J. 2008;25:279–90.

    Article  CAS  Google Scholar 

Download references

Acknowledgment

Our ongoing work on salivary biomarkers is partially funded by research project grants from Indian Council of Medical Research (ICMR, Grant no.: 5/13/95/2003-NCD III) and Gujarat Cancer Society, Ahmedabad (Grant no.: RE/28/BRD 1/09). The authors are also thankful to The Gujarat Cancer and Research Institute for administrative support and allowing to use the clinical material.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Prabhudas S. Patel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shah, F.D., Begum, R., Vajaria, B.N. et al. A Review on Salivary Genomics and Proteomics Biomarkers in Oral Cancer. Ind J Clin Biochem 26, 326–334 (2011). https://doi.org/10.1007/s12291-011-0149-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12291-011-0149-8

Keywords

Navigation