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Open Access 01-12-2014 | Review

A review of research on salivary biomarkers for oral cancer detection

Authors: Yi-Shing Lisa Cheng, Terry Rees, John Wright

Published in: Clinical and Translational Medicine | Issue 1/2014

Abstract

Using saliva for disease diagnostics and health surveillance is a promising approach as collecting saliva is relatively easy and non-invasive. Over the past two decades, using salivary biomarkers specifically for early cancer detection has attracted much research interest, especially for cancers occurring in the oral cavity and oropharynx, for which the five-year survival rate (62%) is still one of the lowest among all major human cancers. More than 90% of oral cancers are oral squamous cell carcinoma (OSCC) and the standard method for detection is through a comprehensive clinical examination by oral healthcare professionals. Despite the fact that the oral cavity is easily accessible, most OSCCs are not diagnosed until an advanced stage, which is believed to be the major reason for the low survival rate, and points to the urgent need for clinical diagnostic aids for early detection of OSCC. Thus, much research effort has been dedicated to investigating potential salivary biomarkers for OSCC, and more than 100 such biomarkers have been reported in the literature. However, some important issues and challenges have emerged that require solutions and further research in order to find reliable OSCC salivary biomarkers for clinical use. This review article provides an up-to-date list of potential OSCC salivary biomarkers reported as of the fall of 2013, and discusses those emerging issues. By raising the awareness of these issues on the part of both researchers and clinicians, it is hoped that reliable, specific and sensitive salivary biomarkers may be found soon—and not only biomarkers for early OSCC detection but also for detecting other types of cancers or even for monitoring non-cancerous disease activity.

Chi AC: Squamous cell carcinoma. In Oral and Maxillofacial Pathology. Edited by: Neville BW, Damm DD, Allen CM, Bouquot JE. St. Louis: Saunders Elsevier; 2009:409–421.

Siegel R, Naishadham D, Jemal A: Cancer statistics, 2013. CA Cancer J Clin 2013, 63(1):11–30. 10.3322/caac.21166CrossRefPubMed

Cheng Y, Wright J: Advances in diagnostic adjuncts for oral squamous cell carcinoma. The Open Pathology Journal 2011, 5: 3–7. 10.2174/1874375701105010003CrossRef

Kalmar JR: Advances in the detection and diagnosis of oral precancerous and cancerous lesions. Oral Maxillofacial Surg Clin N Am 2006, 18: 465–82. 10.1016/j.coms.2006.06.013CrossRef

Patton LL, Epstein JB, Kerr AR: Adjunctive techniques for oral cancer examination and lesion diagnosis: a systematic review of the literature. J Am Dent Assoc 2008, 139(7):896–905. 10.14219/jada.archive.2008.0276CrossRefPubMed

Wong DT: Salivary diagnostics for oral cancer. J Calif Dent Assoc 2006, 34(4):303–8.PubMed

Wong DT: Salivary diagnostics powered by nanotechnologies, proteomics and genomics. J Am Dent Assoc 2006, 137(3):313–21. 10.14219/jada.archive.2006.0180CrossRefPubMed

Castagnola M, Picciotti PM, Messana I, Fanali C, Fiorita A, Cabras T, Calo L, Pisano E, Passali GC, Iavarone F, Paludetti G, Scarano E: Potential applications of human saliva as diagnostic fluid. Acta Otorhinolaryngol Ital 2011, 31(6):347–57.PubMedCentralPubMed

Wu J, Yi C, Chung H, Wang D, Chang W, Lee S, Lin C, Yang Y, Yang W: Potential biomarkers in saliva for oral squamous cell carcinoma. Oral Oncology 2010, 46: 226–31. 10.1016/j.oraloncology.2010.01.007CrossRefPubMed

10.

Zimmermann B, Wong DT: Salivary mRNA targets for cancer diagnostics. Oral Oncol 2008, 44: 425–429. 10.1016/j.oraloncology.2007.09.009PubMedCentralCrossRefPubMed

11.

Nagler RM: Saliva as a tool for oral cancer diagnosis and prognosis. Oral Oncol 2009, 45(12):1006–10. 10.1016/j.oraloncology.2009.07.005CrossRefPubMed

12.

Brinkmann O, Wong DT: Salivary transcriptome biomarkers in oral squamous cell cancer detection. Adv Clin Chem 2011, 55: 21–34.CrossRefPubMed

13.

Zimmermann BG, Park NJ, Wong DT: Genomic targets in saliva. Ann N Y Acad Sci 2007, 1098: 184–91. 10.1196/annals.1384.002PubMedCentralCrossRefPubMed

14.

Zhang A, Sun H, Wang X: Saliva metabolomics opens door to biomarker discovery, disease diagnosis, and treatment. Appl Biochem Biotechnol 2012, 168(6):1718–27. 10.1007/s12010-012-9891-5CrossRefPubMed

15.

Chiappin S, Antonelli G, Gatti R, De Palo EF: Saliva specimen: a new laboratory tool for diagnostic and basic investigation. Clin Chim Acta 2007, 383(1–2):30–40.CrossRefPubMed

16.

Bandhakavi S, Stone MD, Onsongo G, Van Riper SK, Griffin TJ: A dynamic range compression and three-dimensional peptide fractionation analysis platform expands proteome coverage and the diagnostic potential of whole saliva. J Proteome Res 2009, 8(12):5590–600. 10.1021/pr900675wPubMedCentralCrossRefPubMed

17.

Messana I, Inzitari R, Fanali C, Cabras T, Castagnola M: Facts and artifacts in proteomics of body fluids. What proteomics of saliva is telling us? J Sep Sci 2008, 31(11):1948–63. 10.1002/jssc.200800100CrossRefPubMed

18.

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 carcinomas. Oral Oncol 2000, 36(3):272–6. 10.1016/S1368-8375(00)00005-1CrossRefPubMed

19.

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 autoantibodies in sera and saliva of the patients. J Pathol 2000, 192(1):52–7. 10.1002/1096-9896(2000)9999:9999<::AID-PATH669>3.0.CO;2-CCrossRefPubMed

20.

Chen YC, Li TY, Tsai MF: Analysis of the saliva from patients with oral cancer by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 2002, 16(5):364–9. 10.1002/rcm.588CrossRefPubMed

21.

Pickering V, Jordan RC, Schmidt BL: Elevated salivary endothelin levels in oral cancer patients–a pilot study. Oral Oncol 2007, 43(1):37–41. 10.1016/j.oraloncology.2005.12.027CrossRefPubMed

22.

Li Y, St John MA, Zhou X, Kim Y, Sinha U, Jordan RC, Eisele D, Abemayor E, Elashoff D, Park NH, Wong DT: Salivary transcriptome diagnostics for oral cancer detection. Clin Cancer Res 2004, 10(24):8442–50. 10.1158/1078-0432.CCR-04-1167CrossRefPubMed

23.

St John MA, Li Y, Zhou X, Denny P, Ho CM, Montemagno C, Shi W, Qi F, Wu B, Sinha U, Jordan R, Wolinsky L, Park NH, Liu H, Abemayor E, Wong DT: Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 2004, 130(8):929–35. 10.1001/archotol.130.8.929CrossRefPubMed

24.

Rhodus NL, Ho V, Miller CS, Myers S, Ondrey F: NF-kappaB dependent cytokine levels in saliva of patients with oral preneoplastic lesions and oral squamous cell carcinoma. Cancer Detect Prev 2005, 29(1):42–5. 10.1016/j.cdp.2004.10.003CrossRefPubMed

25.

Nagler R, Bahar G, Shpitzer T, Feinmesser R: Concomitant analysis of salivary tumor markers–a new diagnostic tool for oral cancer. Clin Cancer Res 2006, 12(13):3979–84. 10.1158/1078-0432.CCR-05-2412CrossRefPubMed

26.

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(1):54–9. 10.1002/cncr.22386CrossRefPubMed

27.

Vucicevic Boras V, Cikes N, Lukac J, Virag M, Cekic-Arambasin A: Salivary and serum interleukin 6 and basic fibroblast growth factor levels in patients with oral squamous cell carcinoma. Minerva Stomatol 2005, 54(10):569–73.PubMed

28.

Mizukawa N, Sugiyama K, Fukunaga J, Ueno T, Mishima K, Takagi S, Sugahara T: Defensin-1, a peptide detected in the saliva of oral squamous cell carcinoma patients. Anticancer Res 1998, 18(6B):4645–9.PubMed

29.

Hu S, Arellano M, Boontheung P, Wang J, Zhou H, Jiang J, Elashoff D, Wei R, Loo JA, Wong DT: Salivary proteomics for oral cancer biomarker discovery. Clin Cancer Res 2008, 14(19):6246–52. 10.1158/1078-0432.CCR-07-5037PubMedCentralCrossRefPubMed

30.

Almadori G, Bussu F, Galli J, Limongelli A, Persichilli S, Zappacosta B, Minucci A, Paludetti G, Giardina B: Salivary glutathione and uric acid levels in patients with head and neck squamous cell carcinoma. Head Neck 2007, 29(7):648–54. 10.1002/hed.20579CrossRefPubMed

31.

Park NJ, Zhou H, Elashoff D, Henson BS, Kastratovic DA, Abemayor E, Wong DT: Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection. Clin Cancer Res 2009, 15(17):5473–7. 10.1158/1078-0432.CCR-09-0736PubMedCentralCrossRefPubMed

32.

Vajaria BN, Patel KR, Begum R, Shah FD, Patel JB, Shukla SN, Patel PS: Evaluation of serum and salivary total sialic acid and alpha-l-fucosidase in patients with oral precancerous conditions and oral cancer. Oral Surg Oral Med Oral Pathol Oral Radiol 2013, 115(6):764–71. 10.1016/j.oooo.2013.01.004CrossRefPubMed

33.

Liu C, Lin S, Yang C, Cheng H, Chang K: Exploiting salivary miR-31 as a clinical biomarker of oral squamous cell carcinoma. Head Neck 2012, 34: 219–224. 10.1002/hed.21713CrossRefPubMed

34.

Katakura A, Kamiyama I, Takano N, Shibahara T, Muramatsu T, Ishihara K, Takagi R, Shouno T: Comparison of salivary cytokine levels in oral cancer patients and healthy subjects. Bull Tokyo Dent Coll 2007, 48(4):199–203. 10.2209/tdcpublication.48.199CrossRefPubMed

35.

SahebJamee M, Eslami M, AtarbashiMoghadam F, Sarafnejad A: Salivary concentration of TNFalpha, IL1 alpha, IL6, and IL8 in oral squamous cell carcinoma. Med Oral Patol Oral Cir Bucal 2008, 13(5):E292–5.PubMed

36.

Sato J, Goto J, Murata T, Kitamori S, Yamazaki Y, Satob A, Kitagawa Y: Changes in saliva interleukin-6 levels in patients with oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol 2010, 110(3):330–336. 10.1016/j.tripleo.2010.03.040CrossRef

37.

Jiang WW, Masayesva B, Zahurak M, Carvalho AL, Rosenbaum E, Mambo E, Zhou S, Minhas K, Benoit N, Westra WH, Alberg A, Sidransky D, Koch W, Califano J: Increased mitochondrial DNA content in saliva associated with head and neck cancer. Clin Cancer Res 2005, 11(7):2486–91. 10.1158/1078-0432.CCR-04-2147CrossRefPubMed

38.

Cheng Y, Jordan L, Gorugantula L, Schneiderman E, Chen H, Rees T: Salivary interleukins 6 and 8 in oral cancer patients and in patients with chronic oral inflammatory diseases. J of Periodontology in press in press

39.

Gorugantula L, Rees T, Plemons J, Chen H, Cheng Y: Salivary basic fibroblast growth factor in patients with oral squamous cell carcinoma or oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol 2012, 114(2):215–22. 10.1016/j.oooo.2012.03.013PubMedCentralCrossRefPubMed

40.

Cheng YS, Rees T, Jordan L, Oxford L, O'Brien J, Chen HS, Wong D: Salivary endothelin-1 potential for detecting oral cancer in patients with oral lichen planus or oral cancer in remission. Oral Oncol 2011, 47(12):1122–6. 10.1016/j.oraloncology.2011.07.032PubMedCentralCrossRefPubMed

41.

Cheng YS, Jordan L, Rees T, Chen HS, Oxford L, Brinkmann O, Wong D: Levels of potential oral cancer salivary mRNA biomarkers in oral cancer patients in remission and oral lichen planus patients. Clin Oral Investig 2013. Jul 28 [Epub ahead of print] PMID: 23892499 Jul 28 [Epub ahead of print] PMID: 23892499

42.

Carvalho AL, Jeronimo C, Kim MM, Henrique R, Zhang Z, Hoque MO, Chang S, Brait M, Nayak CS, Jiang WW, Claybourne Q, Tokumaru Y, Lee J, Goldenberg D, Garrett-Mayer E, Goodman S, Moon CS, Koch W, Westra WH, Sidransky D, Califano JA: Evaluation of promoter hypermethylation detection in body fluids as a screening/diagnosis tool for head and neck squamous cell carcinoma. Clin Cancer Res 2008, 14(1):97–107. 10.1158/1078-0432.CCR-07-0722CrossRefPubMed

43.

Brinkmann O, Kastratovic DA, Dimitrijevic MV, Konstantinovic VS, Jelovac DB, Antic J, Nesic VS, Markovic SZ, Martinovic ZR, Akin D, Spielmann N, Zhou H, Wong DT: Oral squamous cell carcinoma detection by salivary biomarkers in a Serbian population. Oral Oncol 2011, 47(1):51–5. 10.1016/j.oraloncology.2010.10.009PubMedCentralCrossRefPubMed

44.

Elashoff D, Zhou H, Reiss J, Wang J, Xiao H, Henson B, Hu S, Arellano M, Sinha U, Le A, Messadi D, Wang M, Nabili V, Lingen M, Morris D, Randolph T, Feng Z, Akin D, Kastratovic DA, Chia D, Abemayor E, Wong DT: Prevalidation of salivary biomarkers for oral cancer detection. Cancer Epidemiol Biomarkers Prev 2012, 21(4):664–72. 10.1158/1055-9965.EPI-11-1093PubMedCentralCrossRefPubMed

45.

Jou YJ, Lin CD, Lai CH, Chen CH, Kao JY, Chen SY, Tsai MH, Huang SH, Lin CW: Proteomic identification of salivary transferrin as a biomarker for early detection of oral cancer. Anal Chim Acta 2010, 681(1–2):41–8.CrossRefPubMed

46.

Franzmann EJ, Reategui EP, Pedroso F, Pernas FG, Karakullukcu BM, Carraway KL, Hamilton K, Singal R, Goodwin WJ: Soluble CD44 is a potential marker for the early detection of head and neck cancer. Cancer Epidemiol Biomarkers Prev 2007, 16(7):1348–55. 10.1158/1055-9965.EPI-06-0011CrossRefPubMed

47.

Sugimoto M, Wong DT, Hirayama A, Soga T, Tomita M: Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles. Metabolomics 2010, 6(1):78–95. 10.1007/s11306-009-0178-yPubMedCentralCrossRefPubMed

48.

Wei J, Xie G, Zhou Z, Shi P, Qiu Y, Zheng X, Chen T, Su M, Zhao A, Jia W: Salivary metabolite signatures of oral cancer and leukoplakia. Int J Cancer 2011, 129(9):2207–17. 10.1002/ijc.25881CrossRefPubMed

49.

Shpitzer T, Hamzany Y, Bahar G, Feinmesser R, Savulescu D, Borovoi I, Gavish M, Nagler RM: Salivary analysis of oral cancer biomarkers. Br J Cancer 2009, 101(7):1194–8. 10.1038/sj.bjc.6605290PubMedCentralCrossRefPubMed

50.

Zhong L, Chen G, Xu Z, Zhang X, Ping F, Zhao S: Detection of telomerase activity in saliva from oral squamous cell carcinoma patients. Int J Oral and Maxillofac Surg 2005, 34: 366–370.CrossRef

51.

El-Naggar AK, Mao L, Staerkel G, Coombes MM, Tucker SL, Luna MA, Clayman GL, Lippman S, Goepfert H: Genetic heterogeneity in saliva from patients with oral squamous carcinomas: implications in molecular diagnosis and screening. J Mol Diagn 2001, 3(4):164–70. 10.1016/S1525-1578(10)60668-XPubMedCentralCrossRefPubMed

52.

Agha-Hosseini F, Mirzaii-Dizgah I, Farmanbar N, Abdollahi M: Oxidative stress status and DNA damage in saliva of human subjects with oral lichen planus and oral squamous cell carcinoma. J Oral Pathol Med 2012, 41(10):736–40. 10.1111/j.1600-0714.2012.01172.xCrossRefPubMed

53.

Bernabe DG, Tamae AC, Miyahara GI, Sundefeld ML, Oliveira SP, Biasoli ER: Increased plasma and salivary cortisol levels in patients with oral cancer and their association with clinical stage. J Clin Pathol 2012, 65(10):934–9. 10.1136/jclinpath-2012-200695CrossRefPubMed

54.

He H, Chen G, Zhou L, Liu Y: A joint detection of CEA and CA-50 levels in saliva and serum of patients with tumors in oral region and salivary gland. J Cancer Res Clin Oncol 2009, 135(10):1315–21. 10.1007/s00432-009-0572-xCrossRefPubMed

55.

Shpitzer T, Bahar G, Feinmesser R, Nagler RM: A comprehensive salivary analysis for oral cancer diagnosis. J Cancer Res Clin Oncol 2007, 133(9):613–7. 10.1007/s00432-007-0207-zCrossRefPubMed

56.

Tang H, Wu Z, Zhang J, Su B: Salivary lncRNA as a potential marker for oral squamous cell carcinoma diagnosis. Mol Med Rep 2013, 7(3):761–6.PubMed

57.

Balan JJ, Rao RS, Premalatha BR, Patil S: Analysis of tumor marker CA 125 in saliva of normal and oral squamous cell carcinoma patients: a comparative study. J Contemp Dent Pract 2012, 13(5):671–5.CrossRefPubMed

58.

Shetty SR, Chadha R, Babu S, Kumari S, Bhat S, Achalli S: Salivary lactate dehydrogenase levels in oral leukoplakia and oral squamous cell carcinoma: a biochemical and clinicopathological study. J Cancer Res Ther 2012, 8(Suppl 1):S123–5.PubMed

59.

Jessie K, Jayapalan JJ, Ong KC, Abdul Rahim ZH, Zain RM, Wong KT, Hashim OH: Aberrant proteins in the saliva of patients with oral squamous cell carcinoma. Electrophoresis 2013, 34(17):2495–502. 10.1002/elps.201300107CrossRefPubMed

60.

Jou YJ, Lin CD, Lai CH, Tang CH, Huang SH, Tsai MH, Chen SY, Kao JY, Lin CW: Salivary zinc finger protein 510 peptide as a novel biomarker for detection of oral squamous cell carcinoma in early stages. Clin Chim Acta 2011, 412(15–16):1357–65.CrossRefPubMed

61.

Carvalho AL, Henrique R, Jeronimo C, Nayak CS, Reddy AN, Hoque MO, Chang S, Brait M, Jiang WW, Kim MM, Claybourne Q, Goldenberg D, Khan Z, Khan T, Westra WH, Sidransky D, Koch W, Califano JA: Detection of promoter hypermethylation in salivary rinses as a biomarker for head and neck squamous cell carcinoma surveillance. Clin Cancer Res 2011, 17(14):4782–9. 10.1158/1078-0432.CCR-11-0324PubMedCentralCrossRefPubMed

62.

Contucci AM, Inzitari R, Agostino S, Vitali A, Fiorita A, Cabras T, Scarano E, Messana I: Statherin levels in saliva of patients with precancerous and cancerous lesions of the oral cavity: a preliminary report. Oral Dis 2005, 11(2):95–9. 10.1111/j.1601-0825.2004.01057.xCrossRefPubMed

63.

Hoffmann RR, Yurgel LS, Campos MM: Evaluation of salivary endothelin-1 levels in oral squamous cell carcinoma and oral leukoplakia. Regul Pept 2011, 166(1–3):55–8.CrossRefPubMed

64.

Magnusson M, Pyykko I, van Setten G, Norlander T, Nastri A, Westermark A: Basic fibroblast growth factor (bFGF) in saliva and oral mucosa in patients with oral lichen planus: preliminary observations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004, 98(3):324–6. 10.1016/j.tripleo.2004.02.056CrossRefPubMed

65.

Scully C, Beyli M, Ferreiro MC, Ficarra G, Gill Y, Griffiths M, Holmstrup P, Mutlu S, Porter S, Wray D: Update on oral lichen planus: etiopathogenesis and management. Crit Rev Oral Biol Med 1998, 9(1):86–122. 10.1177/10454411980090010501CrossRefPubMed

66.

Neville BW, Day TA: Oral cancer and precancerous lesions. CA Cancer J Clin 2002, 52(4):195–215. 10.3322/canjclin.52.4.195CrossRefPubMed

67.

Rhodus NL, Cheng B, Myers S, Bowles W, Ho V, Ondrey F: A comparison of the pro-inflammatory, NF-kappaB-dependent cytokines: TNF-alpha, IL-1-alpha, IL-6, and IL-8 in different oral fluids from oral lichen planus patients. Clin Immunol 2005, 114(3):278–83. 10.1016/j.clim.2004.12.003CrossRefPubMed

68.

Teles RP, Likhari V, Socransky SS, Haffajee AD: Salivary cytokine levels in subjects with chronic periodontitis and in periodontally healthy individuals: a cross-sectional study. J Periodontal Res 2009, 44(3):411–7. 10.1111/j.1600-0765.2008.01119.xPubMedCentralCrossRefPubMed

69.

Zhang Y, Lin M, Zhang S, Wang Z, Jiang L, Shen J, Bai J, Gao F, Zhou M, Chen Q: NF-kappaB-dependent cytokines in saliva and serum from patients with oral lichen planus: a study in an ethnic Chinese population. Cytokine 2008, 41(2):144–9. 10.1016/j.cyto.2007.11.004CrossRefPubMed

70.

Arellano-Garcia ME, Hu S, Wang J, Henson B, Zhou H, Chia D, Wong DT: Multiplexed immunobead-based assay for detection of oral cancer protein biomarkers in saliva. Oral Dis 2008, 14(8):705–12. 10.1111/j.1601-0825.2008.01488.xPubMedCentralCrossRefPubMed

71.

Sharma M, Bairy I, Pai K, Satyamoorthy K, Prasad S, Berkovitz B, Radhakrishnan R: Salivary IL-6 levels in oral leukoplakia with dysplasia and its clinical relevance to tobacco habits and periodontitis. Clin Oral Investig 2011, 15(5):705–14. 10.1007/s00784-010-0435-5CrossRefPubMed

72.

Ebersole JL, Schuster JL, Stevens J, Dawson D 3rd, Kryscio RJ, Lin Y, Thomas MV, Miller CS: Patterns of salivary analytes provide diagnostic capacity for distinguishing chronic adult periodontitis from health. J Clin Immunol 2013, 33(1):271–9. 10.1007/s10875-012-9771-3PubMedCentralCrossRefPubMed

73.

Thomas MV, Branscum A, Miller CS, Ebersole J, Al-Sabbagh M, Schuster JL: Within-subject variability in repeated measures of salivary analytes in healthy adults. J Periodontol 2009, 80(7):1146–53. 10.1902/jop.2009.080654PubMedCentralCrossRefPubMed

74.

Kim JK, Zhou H, Nabili V, Wang MB, Abemayor E, Wong DT: Utility of multiple sampling in reducing variation of salivary interleukin-8 and interleukin-1beta mRNA levels in healthy adults. Head Neck 2012, 35(7):968–73.CrossRefPubMed

75.

Jehmlich N, Dinh KH, Gesell-Salazar M, Hammer E, Steil L, Dhople VM, Schurmann C, Holtfreter B, Kocher T, Volker U: Quantitative analysis of the intra- and inter-subject variability of the whole salivary proteome. J Periodontal Res 2012, 48(3):392–403.CrossRefPubMed

76.

Fraser CG: Inherent biological variation and reference values. Clin Chem Lab Med 2004, 42(7):758–64.CrossRefPubMed

77.

Denver R, Tzanidis A, Martin P, Krum H: Salivary endothelin concentrations in the assessment of chronic heart failure. Lancet 2000, 355(9202):468–9. 10.1016/S0140-6736(00)82019-XCrossRefPubMed

78.

Lam HC, Lo GH, Lee JK, Lu CC, Chu CH, Sun CC, Chuang MJ, Wang MC: Salivary immunoreactive endothelin in patients with upper gastrointestinal diseases. J Cardiovasc Pharmacol 2004, 44(Suppl 1):S413–7.CrossRefPubMed

79.

Dodds MW, Johnson DA, Yeh CK: Health benefits of saliva: a review. J Dent 2005, 33(3):223–33. 10.1016/j.jdent.2004.10.009CrossRefPubMed

80.

Denny PC, Denny PA, Klauser DK, Hong SH, Navazesh M, Tabak LA: Age-related changes in mucins from human whole saliva. J Dent Res 1991, 70(10):1320–7. 10.1177/00220345910700100201CrossRefPubMed

81.

Mankan AK, Lawless MW, Gray SG, Kelleher D, McManus R: NF-kappaB regulation: the nuclear response. J Cell Mol Med 2009, 13(4):631–43. 10.1111/j.1582-4934.2009.00632.xPubMedCentralCrossRefPubMed

82.

Hom D: Growth factors in wound healing. Otolaryngol Clin North Am 1995, 28(5):933–53.PubMed

83.

Canakci C, Cicek Y, Yildirim A, Sezer U, Canakci V: Increased levels of 8-hydroxydeoxyguanosine and malondialdehyde and its relationship with antioxidant enzymes in saliva of periodontitis patients. European Journal of Dentistry 2009, 3: 100–106.PubMedCentralPubMed

84.

Gursoy UK, Kononen E, Uitto VJ, Pussinen PJ, Hyvarinen K, Suominen-Taipale L, Knuuttila M: Salivary interleukin-1beta concentration and the presence of multiple pathogens in periodontitis. J Clin Periodontol 2009, 36(11):922–7. 10.1111/j.1600-051X.2009.01480.xCrossRefPubMed

85.

Zhang L, Xiao H, Karlan S, Zhou H, Gross J, Elashoff D, Akin D, Yan X, Chia D, Karlan B, Wong DT: Discovery and preclinical validation of salivary transcriptomic and proteomic biomarkers for the non-invasive detection of breast cancer. PLoS One 2010, 5(12):e15573. 10.1371/journal.pone.0015573PubMedCentralCrossRefPubMed

86.

Xiao H, Zhang L, Zhou H, Lee JM, Garon EB, Wong DT: Proteomic analysis of human saliva from lung cancer patients using two-dimensional difference gel electrophoresis and mass spectrometry. Mol Cell Proteomics 2012, 11(2):M111 012112. 10.1074/mcp.M111.012112PubMedCentralCrossRefPubMed

87.

Bigler LR, Streckfus CF, Dubinsky WP: Salivary biomarkers for the detection of malignant tumors that are remote from the oral cavity. Clin Lab Med 2009, 29(1):71–85. 10.1016/j.cll.2009.01.004CrossRefPubMed

88.

Streckfus C, Bigler L, Tucci M, Thigpen JT: A preliminary study of CA15–3, c-erbB-2, epidermal growth factor receptor, cathepsin-D, and p53 in saliva among women with breast carcinoma. Cancer Invest 2000, 18(2):101–9. 10.3109/07357900009038240CrossRefPubMed

89.

Streckfus C, Bigler L, Dellinger T, Dai X, Kingman A, Thigpen JT: The presence of soluble c-erbB-2 in saliva and serum among women with breast carcinoma: a preliminary study. Clin Cancer Res 2000, 6(6):2363–70.PubMed

90.

Zhang L, Xiao H, Zhou H, Santiago S, Lee JM, Garon EB, Yang J, Brinkmann O, Yan X, Akin D, Chia D, Elashoff D, Park NH, Wong DT: Development of transcriptomic biomarker signature in human saliva to detect lung cancer. Cell Mol Life Sci 2012, 69(19):3341–50. 10.1007/s00018-012-1027-0PubMedCentralCrossRefPubMed

91.

Agha-Hosseini F, Mirzaii-Dizgah I, Rahimi A, Seilanian-Toosi M: Correlation of serum and salivary CA125 levels in patients with breast cancer. J Contemp Dent Pract 2009, 10(6):E001–8.PubMed

92.

Agha-Hosseini F, Mirzaii-Dizgah I, Rahimi A: Correlation of serum and salivary CA15–3 levels in patients with breast cancer. Med Oral Patol Oral Cir Bucal 2009, 14(10):e521–4.CrossRefPubMed

Title: A review of research on salivary biomarkers for oral cancer detection
Authors: Yi-Shing Lisa Cheng
Terry Rees
John Wright
Publication date: 01-12-2014
Publisher: Springer Berlin Heidelberg
Published in: Clinical and Translational Medicine / Issue 1/2014
Electronic ISSN: 2001-1326
DOI: https://doi.org/10.1186/2001-1326-3-3

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A review of research on salivary biomarkers for oral cancer detection

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