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Indian Journal of Clinical Biochemistry

, Volume 26, Issue 4, pp 326–334 | Cite as

A Review on Salivary Genomics and Proteomics Biomarkers in Oral Cancer

  • Franky D. Shah
  • Rasheedunnisa Begum
  • Bhairavi N. Vajaria
  • Kinjal R. Patel
  • Jayendra B. Patel
  • Shilin N. Shukla
  • Prabhudas S. PatelEmail author
Review Article

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.

Keywords

Oral cancer Salivary biomarkers Proteomics Genomics 

Notes

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.

References

  1. 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.CrossRefPubMedGoogle Scholar
  2. 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.CrossRefPubMedGoogle Scholar
  3. 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.CrossRefPubMedGoogle Scholar
  4. 4.
    Boyle P, Levin B, editors. World cancer report 2008. Lyon: International Agency for Research on Cancer; 2008. 330 pp.Google Scholar
  5. 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.CrossRefPubMedGoogle Scholar
  6. 6.
    Slaughter DL, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium: clinical implication of multicentric origins. Cancer. 1953;6:963–8.CrossRefPubMedGoogle Scholar
  7. 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.CrossRefPubMedGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. 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.Google Scholar
  10. 10.
    Messadi DV, Wilder SP, Wolinsky L. Improving oral cancer survival: the role of dental providers. J Calif Dent Assoc. 2009;37:789–98.PubMedGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 12.
    Leston JS, Dios PD. Diagnostic clinical aids in oral cancer. Oral Oncol. 2010;46:418–22.CrossRefGoogle Scholar
  13. 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.CrossRefGoogle Scholar
  14. 14.
    Cassolato SF, Turnbull RS. Xerostomia: clinical aspects and treatment. Gerodontology. 2003;20:64–77.CrossRefPubMedGoogle Scholar
  15. 15.
    Brosky ME. The role of saliva in oral health: strategies for prevention and management of xerostomia. J Support Oncol. 2007;5:215–25.PubMedGoogle Scholar
  16. 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. 17.
    Zimmermann BG, Park NJ, Wong DT. Genomic targets in saliva. Ann NY Acad Sci. 2007;1098:184–91.CrossRefPubMedGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 19.
    Wong DT. Salivary diagnostics powered by nanotechnologies, proteomics and genomics. J Am Dent Assoc. 2006;137:313–21.PubMedGoogle Scholar
  20. 20.
    Streckfus CF, Dubinsky WP. Proteomic analysis of saliva for cancer diagnosis. Expert Rev Proteomics. 2007;4:329–32.CrossRefPubMedGoogle Scholar
  21. 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.CrossRefGoogle Scholar
  22. 22.
    Chen DX, Schwartz PE, Li FQ. Salivary and serum CA 125 assays for detecting malignant ovarian tumors. Obstet Gynecol. 1990;75:701–14.PubMedGoogle Scholar
  23. 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.CrossRefPubMedGoogle Scholar
  24. 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.CrossRefPubMedGoogle Scholar
  25. 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. 26.
    Nagler RM. Saliva as a tool for oral cancer diagnosis and prognosis. Oral Oncol. 2009;45:1006–16.CrossRefPubMedGoogle Scholar
  27. 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.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 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.CrossRefPubMedGoogle Scholar
  30. 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.CrossRefPubMedGoogle Scholar
  31. 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.CrossRefGoogle Scholar
  32. 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.CrossRefPubMedGoogle Scholar
  33. 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.CrossRefPubMedGoogle Scholar
  34. 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.PubMedGoogle Scholar
  35. 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.CrossRefPubMedGoogle Scholar
  36. 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.CrossRefPubMedGoogle Scholar
  37. 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.CrossRefPubMedGoogle Scholar
  38. 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.CrossRefPubMedGoogle Scholar
  39. 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.CrossRefPubMedGoogle Scholar
  40. 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.CrossRefPubMedGoogle Scholar
  41. 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.CrossRefPubMedGoogle Scholar
  42. 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.CrossRefPubMedGoogle Scholar
  43. 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.CrossRefPubMedGoogle Scholar
  44. 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.CrossRefPubMedGoogle Scholar
  45. 45.
    Zimmermann BG, Wong DT. Salivary mRNA targets for cancer diagnostics. Oral Oncol. 2008;44:425–9.CrossRefPubMedGoogle Scholar
  46. 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.CrossRefGoogle Scholar
  47. 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.CrossRefPubMedGoogle Scholar
  48. 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.PubMedGoogle Scholar
  49. 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.CrossRefPubMedGoogle Scholar
  50. 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.CrossRefPubMedGoogle Scholar
  51. 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.CrossRefPubMedGoogle Scholar
  52. 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.CrossRefPubMedGoogle Scholar
  53. 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.CrossRefPubMedGoogle Scholar
  54. 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.CrossRefGoogle Scholar
  55. 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.CrossRefPubMedGoogle Scholar
  56. 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.PubMedGoogle Scholar
  57. 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.CrossRefPubMedGoogle Scholar
  58. 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.CrossRefPubMedGoogle Scholar
  59. 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.CrossRefGoogle Scholar
  60. 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.PubMedGoogle Scholar
  61. 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.CrossRefPubMedGoogle Scholar
  62. 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.CrossRefPubMedGoogle Scholar
  63. 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.CrossRefGoogle Scholar

Copyright information

© Association of Clinical Biochemists of India 2011

Authors and Affiliations

  • Franky D. Shah
    • 1
  • Rasheedunnisa Begum
    • 2
  • Bhairavi N. Vajaria
    • 1
  • Kinjal R. Patel
    • 1
  • Jayendra B. Patel
    • 1
  • Shilin N. Shukla
    • 3
  • Prabhudas S. Patel
    • 1
    Email author
  1. 1.Biochemistry Research DivisionThe Gujarat Cancer & Research InstituteAhmedabadIndia
  2. 2.Biochemistry DepartmentM.S. University of BarodaVadodaraIndia
  3. 3.The Gujarat Cancer & Research InstituteAhmedabadIndia

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