Volume 11, Issue 2 (Vol.11 No.2 Jul 2022)                   rbmb.net 2022, 11(2): 200-208 | Back to browse issues page


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Department of Oral and Maxillofacial Pathology, School of Dentistry, Golestan University of Medical Sciences, Gorgan, Iran.
Abstract:   (1970 Views)
Background: The oral squamous cell carcinoma (OSCC) composes about 90% of all head and neck cancers. The toll-like receptor (TLR)+ immune cells have potential of invasion and malignancy transformation. The aim of this study was assessment of possible associations between clinicopathological indices and TLR2 and TLR9 gene expression in OSCC.

Methods: Forty-two OSCC samples with related healthy margins including 25 early and 17 advanced stages were gathered. The samples were classified histologically from grade I to II. The expression of TLR2 and TLR2 was evaluated by Real-time PCR. The patient’s disease-free survival (DFS) and overall survival (OS) were analyzed using SPSS V.23 software.

Results: The expression of TLR2 and TLR9 genes in tumor tissues (especially in grade I and II) were higher than healthy surgical margin tissue (p< 0.001). TLR9 expression in grade II was statistically significant than grade I in tumor tissue (p< 0.001). TLR9 expression in advanced stage was statistically significant in compare to early stage (p= 0.012). In advanced stage both overall survival (p= 0.029) and disease-free survival (p= 0.012) were statistically lower than early stage. The follow-up time to recurrence in advanced stage was statistically lower than early stage (p= 0.007).

Conclusions: Overexpression of TLRs 2, 9 play role in the pathogenesis and tumor development of OSCC and can be applied as biomarker in prognostic approaches.
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Type of Article: Original Article | Subject: Molecular Biology
Received: 2021/12/22 | Accepted: 2021/12/25 | Published: 2022/08/7

References
1. Cramer JD, Burtness B, Le QT, Ferris RL. The changing therapeutic landscape of head and neck cancer. Nat Rev Clin Oncol. 2019;16(11):669-683. [DOI:10.1038/s41571-019-0227-z] [PMID]
2. Miyauchi S, Kim SS, Pang J, Gold KA, Gutkind JS, Califano JA, et al. Immune Modulation of Head and Neck Squamous Cell Carcinoma and the Tumor Microenvironment by Conventional Therapeutics. Clin Cancer Res. 2019;25(14):4211-4223. [DOI:10.1158/1078-0432.CCR-18-0871] [PMID] [PMCID]
3. Mohtasham N, Mahdavi-Shahri N, Salehinejad J, Ejtehadi H, Torabi-Parizi M, Ghazi N. Detection of nucleoproteins in squamous cell carcinoma, and dysplastic and normal mucosa in the oral cavity by methyl green-pyronin staining. J Oral Sci. 2010;52(2):239-43. [DOI:10.2334/josnusd.52.239] [PMID]
4. Jang GY, Lee JW, Kim YS, Lee SE, Han HD, Hong KJ, et al. Interactions between tumor-derived proteins and Toll-like receptors. Exp Mol Med. 2020;52(12):1926-1935. [DOI:10.1038/s12276-020-00540-4] [PMID] [PMCID]
5. Li D, Wu M. Pattern recognition receptors in health and diseases. Signal Transduct Target Ther. 202;6(1):291. [DOI:10.1038/s41392-021-00687-0] [PMID] [PMCID]
6. Sharma Y, Bala K. Role of Toll like receptor in progression and suppression of oral squamous cell carcinoma. Oncol Rev. 2020;14(1):456. [DOI:10.4081/oncol.2020.456] [PMID] [PMCID]
7. Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2:17023. [DOI:10.1038/sigtrans.2017.23] [PMID] [PMCID]
8. Mohajertehran F, Ghodsi K, Hafizi L, Rezaee A. Frequency and the type of chromosomal abnormalities in patients with primary amenorrhea in northeast of iran. Iran J Basic Med Sci. 2013;16(4):643-639.
9. Urban-Wojciuk Z, Khan MM, Oyler BL, Fåhraeus R, Marek-Trzonkowska N, Nita-Lazar A, et al. The Role of TLRs in Anti-cancer Immunity and Tumor Rejection. Front Immunol. 2019;10:2388. [DOI:10.3389/fimmu.2019.02388] [PMID] [PMCID]
10. Basith S, Manavalan B, Yoo TH, Kim SG, Choi S. Roles of toll-like receptors in cancer: a double-edged sword for defense and offense. Arch Pharm Res. 2012;35(8):1297-316. [DOI:10.1007/s12272-012-0802-7] [PMID]
11. Sim YC, Hwang JH, Ahn KM. Overall and disease-specific survival outcomes following primary surgery for oral squamous cell carcinoma: analysis of consecutive 67 patients. J Korean Assoc Oral Maxillofac Surg. 2019;45(2):83-90. [DOI:10.5125/jkaoms.2019.45.2.83] [PMID] [PMCID]
12. Mohajertehran F, Ayatollahi H, Jafarian AH, Khazaeni K, Soukhtanloo M, Shakeri MT, et al. Overexpression of Lactate Dehydrogenase in the Saliva and Tissues of Patients with Head and Neck Squamous Cell Carcinoma. Rep Biochem Mol Biol. 2019;7(2):142-149.
13. Mohtasham N, Ayatollahi H, Saghravanian N, Zare R, Shakeri MT, Sahebkar A, et al. Evaluation of Tissue and Serum Expression Levels of Lactate Dehydrogenase Isoenzymes in Patients with Head and Neck Squamous Cell Carcinoma. Anticancer Agents Med Chem. 2019;19(17):2072-2078. [DOI:10.2174/1871520619666191014160818] [PMID]
14. Mohtasham N, Babakoohi S, Montaser-Kouhsari L, Memar B, Salehinejad J, Rahpeyma A, et al. The expression of heat shock proteins 27 and 105 in squamous cell carcinoma of the tongue and relationship with clinicopathological index. Med Oral Patol Oral Cir Bucal. 2011;16(6):e730-5. [DOI:10.4317/medoral.17007] [PMID]
15. Bugshan A, Farooq I. Oral squamous cell carcinoma: metastasis, potentially associated malignant disorders, etiology and recent advancements in diagnosis. F1000Res. 2020;9:229. [DOI:10.12688/f1000research.22941.1] [PMID] [PMCID]
16. Rich AM, Hussaini HM, Parachuru VP, Seymour GJ. Toll-like receptors and cancer, particularly oral squamous cell carcinoma. Front Immunol. 2014;5:464. [DOI:10.3389/fimmu.2014.00464] [PMID] [PMCID]
17. Parroche P, Roblot G, Le Calvez-Kelm F, Tout I, Marotel M, Malfroy M, et al. TLR9 re-expression in cancer cells extends the S-phase and stabilizes p16(INK4a) protein expression. Oncogenesis. 2016;5(7):e244. [DOI:10.1038/oncsis.2016.49] [PMID] [PMCID]
18. Hsiao JR, Chang CC, Lee WT, Huang CC, Ou CY, Tsai ST, et al. The interplay between oral microbiome, lifestyle factors and genetic polymorphisms in the risk of oral squamous cell carcinoma. Carcinogenesis. 2018;39(6):778-787. [DOI:10.1093/carcin/bgy053] [PMID]
19. Wu JF, Chen CH, Ni YH, Lin YT, Chen HL, Hsu HY, et al. Toll-like receptor and hepatitis B virus clearance in chronic infected patients: a long-term prospective cohort study in Taiwan. J Infect Dis. 2012;206(5):662-8. [DOI:10.1093/infdis/jis420] [PMID]
20. Jahanbin A, Hasanzadeh N, Abdolhoseinpour F, Sadr-Nabavi A, Raisolsadat MA, Shamsian K, et al. Analysis of MTHFR Gene C.677C>T and C.1298A>C Polymorphisms in Iranian Patients with Non-Syndromic Cleft Lip and Palate. Iran J Public Health. 2014;43(6):821-7.
21. Zeljic K, Supic G, Jovic N, Kozomara R, Brankovic-Magic M, Obrenovic M, et al. Association of TLR2, TLR3, TLR4 and CD14 genes polymorphisms with oral cancer risk and survival. Oral Dis. 2014;20(4):416-24. [DOI:10.1111/odi.12144] [PMID]
22. Mohtasham N, Anvari K, Memar B, Saghravanian N, Ghazi N, Bagherpour A, et al. Expression of E-cadherin and matrix metalloproteinase-9 in oral squamous cell carcinoma and histologically negative surgical margins and association with clinicopathological parameters. Rom J Morphol Embryol. 2014;55(1):117-21.
23. Salehinejad J, Mohtasham N, Bagherpour A, Abbaszadeh-Bidokhty H, Ghazi A. Evaluation of c-kit protein (CD117) expression in common salivary gland neoplasms. J Oral Maxillofac Pathol. 2014;18(2):177-82. [DOI:10.4103/0973-029X.140732] [PMID] [PMCID]
24. Pacini L, Savini C, Ghittoni R, Saidj D, Lamartine J, Hasan UA, et al. Downregulation of Toll-Like Receptor 9 Expression by Beta Human Papillomavirus 38 and Implications for Cell Cycle Control. J Virol. 2015;89(22):11396-405. [DOI:10.1128/JVI.02151-15] [PMID] [PMCID]
25. Mäkinen LK, Atula T, Häyry V, Jouhi L, Datta N, Lehtonen S, et al. Predictive role of Toll-like receptors 2, 4, and 9 in oral tongue squamous cell carcinoma. Oral Oncol. 2015;51(1):96-102. [DOI:10.1016/j.oraloncology.2014.08.017] [PMID]
26. Branchi V, Esser L, Boden C, Jafari A, Henn J, Lingohr P, et al. A Combined TLR7/TLR9/GATA3 Score Can Predict Prognosis in Biliary Tract Cancer. Diagnostics (Basel). 2021;11(9):1597. [DOI:10.3390/diagnostics11091597] [PMID] [PMCID]
27. Wild CA, Brandau S, Lindemann M, Lotfi R, Hoffmann TK, Lang S, et al. Toll-like Receptors in Regulatory T Cells of Patients With Head and Neck Cancer. Arch Otolaryngol Head Neck Surg. 2010;136(12):1253-9. [DOI:10.1001/archoto.2010.195]
28. Hussaini HM, Parachuru VPB, Seymour GJ, Rich AM. Forkhead box-P3(+) regulatory T cells and toll-like receptor 2 co-expression in oral squamous cell carcinoma. Acta Histochem. 2017;119(3):205-210. [DOI:10.1016/j.acthis.2016.12.005] [PMID]
29. Ng LK, Rich AM, Hussaini HM, Thomson WM, Fisher AL, Horne LS, et al. Toll-like receptor 2 is present in the microenvironment of oral squamous cell carcinoma. Br J Cancer. 2011;104(3):460-3. [DOI:10.1038/sj.bjc.6606057] [PMID] [PMCID]
30. Sato-Kaneko F, Yao S, Ahmadi A, Zhang SS, Hosoya T, Kaneda MM, et al. Combination immunotherapy with TLR agonists and checkpoint inhibitors suppresses head and neck cancer. JCI Insight. 2017;2(18):e93397. [DOI:10.1172/jci.insight.93397] [PMID] [PMCID]

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