Oral Kanserlerin Tanısında Tükürük Biyobelirteçlerinin Rolü

Öz

ÖZ Oral kanserlerin görülme sıklığı tüm dünyada artış göstermektedir. Dünyada en sık görülen altıncı kanser olup, baş ve boyun bölgesinde larinks kanserinden sonra en sık görülen ikinci kanser türüdür. Hastayı hekime getiren uyarı işaretlerinden ağrı, ağız kanserlerinde görülen ana semptomlardan biri olmasına rağmen ne yazık ki genellikle lezyonlar ciddi boyuta ulaştıktan sonra hissedilir. Bu yüzden erken tanı hastalığın prognozu açısından oldukça önemlidir. Biyopsi, hastalığın erken teşhisinde altın standart kabul edilse de son yıllarda gelişen moleküler klinik teşhis yöntemleri dikkatleri tükürüğün üzerine çekmiştir. Tükürüğün, klinik ve translasyonel uygulamalar için potansiyel biyobelirteç olabilecek çeşitli metabolitler içermesi ve non-invaziv bir yöntem olması kanser teşhisinde ‘’kan yerine tükürük tercih edilebilir mi? sorusunu akla getirmektedir. Tükürük tanı amacıyla ilk kez 1986 yılında Jenzano ve arkadaşları tarafından uzak tümörleri taramak için kullanıldı. Sonraki yıllarda yapılan çalışmalarda da çeşitli maligniteler ve sistemik hastalıklar için tükürükteki spesifik biyobelirteçlerin arayışı başladı. Biz de bu derlemede güncel literatür ışığında ulaşılması kolay ve özel çözünebilir belirteçlerden (markerlardan) zengin olan tükürüğün oral kanserlerin erken teşhisindeki rolünden bahsettik. Anahtar Sözcükler: Biyobelirteç, Oral kanser, Skuamöz hücreli karsinom, Tükürük

Anahtar Kelimeler

• Biyobelirteç
• oral kanser
• skuamöz hücreli karsinom
• tükürük

The Role of Saliva Biomarkers in the Diagnosis of Oral Cancers

Abstract

ABSTRACT The incidence of oral cancers is increasing all over the world. It is the 6th most common cancer in the world and is the second most common cancer in the head and neck region after laryngeal cancer. Although pain, one of the warning signs that brings the patient to the physician, is one of the main symptoms seen in oral cancers, unfortunately it’s usually felt after the lesions reach a serious size. Early diagnosis is very important for the prognosis of the disease. Although biopsy is considered the gold standard in the early diagnosis of the disease, molecular clinicaldiagnostic methods developed in recent years have attracted attention to saliva. Given the fact saliva is a non-invasive method and contains various metabolites that can be potential biomarkers for clinical and translational applications, raises a question ‘’ Can saliva be preferred over blood ?’’.Saliva was first used for diagnostic purposes in 1986 by Jenzano et al. to screen distant tumors. In subsequent studies, the search for specific biomarkers in saliva began for various malignancies and systemic diseases In this review, we refer to the role of saliva, which is easy to access and rich in soluble markers in the early diagnosis of oral cancers in the light of current literature. Key Words: Biomarker, Oral cancer, Saliva, Squamous cell carcinoma

Keywords

• Biomarker
• oral cancer
• saliva
• squamous cell carcinoma

Kaynakça

1. 1. Yazar H, Karaca İR. Oral kavitede görülen invaziv kanserler: derleme. Invasive Cancers Oral Cavity Rev. 2018;10(4):523-9.
2. 2. Oral Dijital Atlas - Katkıda Bulunanlar [İnternet]. [a.yer 07 Temmuz 2020]. Erişim adresi: https://screening.iarc.fr/atlasoralcontrib.php
3. 3. Oral Cancer: The Dentist’s Role in Diagnosis, Management, Rehabilitation, and Prevention [İnternet]. [a.yer 23 Ağustos 2020]. Erişim adresi: http://www.quintpub.com/display_detail.php3?psku=B3571#.X0KKwMgza00
4. 4. Scully C, Bagan J. Oral squamous cell carcinoma overview. Oral Oncol. 2009;45(4):301-8.
5. 5. A digital manual for the early diagnosis of oral neoplasia [İnternet]. [a.yer 07 Temmuz 2020]. Erişim adresi: https://screening.iarc.fr/atlasoral_list.php?cat=B2&lang=1
6. 6. Cancer today [Internet]. [a.yer 26 Ekim 2020]. Erişim adresi: http://gco.iarc.fr/today/home
7. 7. Tanyeri̇ H, Ofluoğlu D, Karataşli G, Yilmazer R. Oral kanserlerin erken teşhisinde diş hekimlerinin rolü: iki olgu nedeniyle. J Istanb Univ Fac Dent.2010;42(3-4):11-6.
8. 8. Oygür T. Ağız patolojisi ders kitabı [İnternet]. Eflatun Basım Dağıtım Yayıncılık; 2018. Erişim adresi: https://books.google.com.tr/books?id=IKtXDwAAQBAJ

9. 9. Kayhan KB, ÜNÜR M. Oral Cavity Cancers and Classification. Istanb Üniversitesi Hekim Fakültesi Derg Istanb. 2011;45(1):55-63.
10. 10. Llewellyn CD, Johnson NW, Warnakulasuriya KA. Risk factors for squamous cell carcinoma of the oral cavity in young people--a comprehensive literature review. Oral Oncol. 2001;37(5):401-18.
11. 11. Ko YC, Huang YL, Lee CH, Chen MJ, Lin LM, Tsai CC. Betel quid chewing, cigarette smoking and alcohol consumption related to oral cancer in Taiwan. J Oral Pathol Med Off Publ Int Assoc Oral Pathol Am Acad Oral Pathol. 1995;24(10):450-3.
12. 12. Chi AC, Day TA, Neville BW. Oral cavity and oropharyngeal squamous cell carcinoma-an update: Oral & Oropharyngeal Cancer Update. CA Cancer J Clin. 2015;65(5):401-21. 13. Rumboldt Z, Gordon L, Gordon L, Bonsall R, Ackermann S. Imaging in head and neck cancer. Curr Treat Options Oncol. 2006;7(1):23-34.
13. 14. Jenzano JW, Courts NF, Timko DA, Lundblad RL. Levels of Glandular Kallikrein in Whole Saliva Obtained from Patients with Solid Tumors Remote from the Oral Cavity. J Dent Res. 1986;65(1):67-70. 15. Radhika T, Jeddy N, Nithya S, Muthumeenakshi RM. Salivary biomarkers in oral squamous cell carcinoma - An insight. J Oral Biol Craniofacial Res.2016;6(Suppl 1):S51-4.
14. 16. Wang X, Kaczor-Urbanowicz KE, Wong DTW. Salivary biomarkers in cancer detection. Med Oncol. 2017;34(1):7.
15. 17. Edgar WM. Saliva and dental health. Clinical implications of saliva: report of a consensus meeting. Br Dent J.1990;169(3-4):96-8.
16. 18. Johnson LR. Gastrointestinal Physiology E-Book. Elsevier Health Sciences; 2018. 170 s.
17. 19. Schrohl A-S, Würtz S, Kohn E, Banks RE, Nielsen HJ, Sweep FCGJ, vd. Banking of Biological Fluids for Studies of Disease-associated Protein Biomarkers. Mol Amp Cell Proteomics.2008;7(10):2061.
18. 20. Lehto V-P, Pontén J. Tumor Markers in Human Biopsy Material. Acta Oncol. 1989;28(5):743-63.
19. 21. Pesce AJ, Kaplan LA. Clinical chemistry : theory, analysis and correlation. 1984.
20. 22. Dx C, Pe S, Fq L. Saliva and serum CA 125 assays for detecting malignant ovarian tumors. Obstet Gynecol.1990;75(4):701-4.
21. 23. C S, L B, M T, Jt T. A preliminary study of CA15-3, c-erbB-2, epidermal growth factor receptor, cathepsin-D, and p53 in saliva among women with breast carcinoma [Internet]. C. 18, Cancer investigation. Cancer Invest; 2000 [a.yer 14 Ekim 2020]. Erişim adresi: https://pubmed.ncbi.nlm.nih.gov/10705871/
22. 24. Schapher M, Wendler O, Gröschl M, Schäfer R, Iro H, Zenk J. Salivary Leptin as a Candidate Diagnostic Marker in Salivary Gland Tumors. Clin Chem. 2009;55(5):914-22.
23. 25. Zhang L, Farrell JJ, Zhou H, Elashoff D, Akin D, Park N, vd. Salivary Transcriptomic Biomarkers for Detection of Resectable Pancreatic Cancer. Gastroenterology. 2010;138(3):949-957.e7.
24. 26. Shah FD, Begum R, Vajaria BN, Patel KR, Patel JB, Shukla SN, vd. A Review on Salivary Genomics and Proteomics Biomarkers in Oral Cancer. Indian J Clin Biochem. 2011;26(4):326-34.
25. 27. Wong DTW. Salivaomics. J Am Dent Assoc 1939. 2012;143(10 Suppl):19S-24S.
26. 28. Yoshizawa JM, Schafer CA, Schafer JJ, Farrell JJ, Paster BJ, Wong DTW. Salivary Biomarkers: Toward Future Clinical and Diagnostic Utilities. Clin Microbiol Rev. 2013;26(4):781-91.
27. 29. 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.
28. 30. Yu J-S, Chen Y-T, Chiang W-F, Hsiao Y-C, Chu LJ, See L-C, vd. Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan. Proc Natl Acad Sci. 2016;113(41):11549-54. 31. Khurshid Z, Zafar MS, Khan RS, Najeeb S, Slowey PD, Rehman IU. Role of Salivary Biomarkers in Oral Cancer Detection. Adv Clin Chem. 2018;86:23-70.
29. 32. Nagler RM. Saliva as a tool for oral cancer diagnosis and prognosis. Oral Oncol. 2009;45(12):1006-10.
30. 33. Wu CC, Chu HW, Hsu CW, Chang KP, Liu HP. Saliva proteome profiling reveals potential salivary biomarkers for detection of oral cavity squamous cell carcinoma. Proteomics. 2015 ;15(19):3394-404.
31. 34. Rosin MP, Cheng X, Poh C, Lam WL, Huang Y, Lovas J, Berean K, Epstein JB, Priddy R, Le ND, Zhang L. Use of allelic loss to predict malignant risk for low-grade oral epithelial dysplasia. Clin Cancer Res. 2000 ;6(2):357-62.
32. 35. Rosas SL, Koch W, da Costa Carvalho MG, Wu L, Califano J, Westra W, Jen J, Sidransky D. Promoter hypermethylation patterns of p16, O6-methylguanine-DNA-methyltransferase, and death-associated protein kinase in tumors and saliva of head and neck cancer patients. Cancer Res. 2001,1;61(3):939-42.
33. 36. Zhong L-P, Chen G-F, Xu Z-F, Zhang X, Ping F-Y, Zhao S-F. Detection of telomerase activity in saliva from oral squamous cell carcinoma patients. Int J Oral Maxillofac Surg. 2005;34(5):566-70.
34. 37. Shpitzer T, Hamzany Y, Bahar G, Feinmesser R, Savulescu D, Borovoi I, vd. Salivary analysis of oral cancer biomarkers. Br J Cancer. 2009;101(7):1194-8.
35. 38. Park NJ, Zhou H, Elashoff D, Henson BS, Kastratovic DA, Abemayor E, vd. Salivary microRNA: Discovery, Characterization, and Clinical Utility for Oral Cancer Detection. Clin Cancer Res. 2009;15(17):5473-7.
36. 39. Mattick JS. Non-coding RNAs: the architects of eukaryotic complexity. EMBO Rep. 2001;2(11):986-91.
37. 40. Wong DTW. Salivary Extracellular Noncoding RNA: Emerging Biomarkers for Molecular Diagnostics. Clin Ther. 2015;37(3):540-51.
38. 41. Panta P, Venna VR. Salivary RNA signatures in oral cancer detection. Anal Cell Pathol Amst. 2014;2014:450629.
39. 42. Liu CJ, Lin SC, Yang CC, Cheng HW, Chang KW. Exploiting salivary miR-31 as a clinical biomarker of oral squamous cell carcinoma. Head Neck. 2012;34(2):219-24.
40. 43. Zahran F, Ghalwash D, Shaker O, Al-Johani K, Scully C. Salivary microRNAs in oral cancer. Oral Dis. 2015 ;21(6):739-47.
41. 44. Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, Galas DJ, Wang K. The microRNA spectrum in 12 body fluids. Clin Chem. 2010 ;56(11):1733-41.
42. 45. Adami GR, Adami AJ. Looking in the mouth for noninvasive gene expression-based methods to detect oral, oropharyngeal, and systemic cancer. ISRN Oncol. 2012;2012:931301.
43. 46. Franzmann EJ, Reategui EP, Pedroso F, Pernas FG, Karakullukcu BM, Carraway KL, vd. Soluble CD44 is a potential marker for the early detection of head and neck cancer. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol. 2007;16(7):1348-55.
44. 47. St John MAR, Li Y, Zhou X, Denny P, Ho C-M, Montemagno C, vd. 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.