Immunohistochemical Expression of SIRT1 in Oral Squamous Cell Carcinoma and its Relationship with Clinical-Pathological Factors
Keywords:Squamous cell carcinoma, Immunohistochemical staining, SIRT1
Objective: Oral squamous cell carcinoma (OSCC) is the most common oral cancer in the world that threatens public health. There are a number of molecular markers that can be used to improve TNM staging. One of these markers is SIRT1. We aimed to investigate the expression of SIRT1 in OSCC and its relationship with clinicopathological factors such as age, sex, location of tumor, smoking, clinical stage, grade of tumor, metastasis to lymph nodes in the neck and distant metastasis.
Methods: This cross-sectional study was performed on 30 samples of OSCC and 30 samples of normal oral mucosa. Required clinical data were collected from patients. After immunohistochemistry staining for SIRT1 on sections prepared with paraffin blocks, the percentage of stained cells and staining intensity of the cells were evaluated in the terms of core and cytoplasmic aspects.
Results: Positive expression of SIRT1 was seen in 93.3% and 96.7% of cells in the core and cytoplasm view, respectively, which was significantly higher than normal tissue (P=0.021 and 0.001, respectively). We found no significant relationship between the intensity and percentage of core and cytoplasmic staining of squamous cells as well as clinicopathological factors.
Conclusion: The overexpression of SIRT1 in OSCC samples as compared with normal mouth tissue indicates its role in carcinogenesis. However, further studies on SIRT1 may shed more light on the treatment options of OSCC.
2. Noch EK, Khalili K. The role of AEG-1/MTDH/LYRIC in the pathogenesis of central nervous system disease. Adv Cancer Res. 2013;120:159-192.
3. Noguchi A, Li X, Kubota A, Kikuchi K, Kameda Y, Zheng H, et al. SIRT1 expression is associated with good prognosis for head and neck squamous cell carcinoma patients. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;115(3):385-392.
4. Seyedmajidi M, Shafaee S, Siadati S, Khorasani M, Bijani A, Ghasemi N. Cyclo-oxygenase-2 expression in oral squamous cell carcinoma. J Can Res Ther. 2014;10(4):1024-1029.
5. Shakib PA, Ensani F, Abdirad A, Valizadeh B, Seyedmajidi M, Sum S. CD44 and CD74: The promising candidates for molecular targeted therapy in oral squamous cell carcinoma. Dent Res J (Isfahan). 2015;12(2):181-186.
6. Emdad L, Das SK, Dasgupta S, Hu B, Sarkar D, Fisher PB. AEG-1/MTDH/LYRIC: signaling pathways, downstream genes, interacting proteins, and regulation of tumor angiogenesis. Adv Cancer Res. 2013;120:75-111.
7. Longo VD, Kennedy BK. Sirtuins in aging and age-related disease. Cell. 2006;126(2):257-268.
8. Murayama A, Ohmori K, Fujimura A, Minami H, Yasuzawa-Tanaka K, Kuroda T, et al. Epigenetic control of rDNA loci in response to intracellular energy status. Cell. 2008;133(4):627-639.
9. Bosch-Presegue L, Vaquero A. The dual role of sirtuins in cancer. Genes Cancer. 2011;2(6):648-662.
10. Liu T, Liu PY, Marshall GM. The critical role of the class III histone deacetylase SIRT1 in cancer. Cancer Res. 2009;69(5):1702-1705.
11. van der Schroeff MP, van Schie K, Langeveld TP, Looman C, Baatenburg de Jong RJ. Model-assisted predictions on prognosis in HNSCC: do we learn? Eur Arch Otorhinolaryngol. 2010;267(9):1445-1448.
12. Emdad L, Sarkar D, Su ZZ, Lee SG, Kang DC, Bruce JN, et al. Astrocyte elevated gene-1: recent insights into a novel gene involved in tumor progression, metastasis and neurodegeneration. Pharmacol Ther. 2007;114(2):155-170.
13. Jung W, Hong KD, Jung WY, Lee E, Shin BK, Kim HK, et al. SIRT1 Expression Is Associated with Good Prognosis in Colorectal Cancer. Korean J Pathol. 2013;47(4):332-339.
14. Jin Q, Yan T, Ge X, Sun C, Shi X, Zhai Q. Cytoplasm-localized SIRT1 enhances apoptosis. J Cell Physiol. 2007;213(1):88-97.
15. Hida Y, Kubo Y, Murao K, Arase S. Strong expression of a longevity-related protein, SIRT1, in Bowen's disease. Arch Dermatol Res. 2007;299(2):103-106.
16. Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell. 2005;16(10):4623-4635.
17. Lai CC, Lin PM, Lin SF, Hsu CH, Lin HC, Hu ML, et al. Altered expression of SIRT gene family in head and neck squamous cell carcinoma. Tumour Biol. 2013;34(3):1847-1854.
18. Byles V, Chmilewski LK, Wang J, Zhu L, Forman LW, Faller DV, et al. Aberrant cytoplasm localization and protein stability of SIRT1 is regulated by PI3K/IGF-1R signaling in human cancer cells. Int J Biol Sci. 2010;6(6):599-612.
19. Yu DF, Jiang SJ, Pan ZP, Cheng WD, Zhang WJ, Yao XK, et al. Expression and clinical significance of Sirt1 in colorectal cancer. Oncol Lett. 2016;11(2):1167-1172.
20. Lee H, Kim KR, Noh SJ, Park HS, Kwon KS, Park BH, et al. Expression of DBC1 and SIRT1 is associated with poor prognosis for breast carcinoma. Hum Pathol. 2011;42(2):204-13.
21. Lin SY, Peng F. Association of SIRT1 and HMGA1 expression in non-small cell lung cancer. Oncol Lett. 2016;11(1):782-788.
22. Kabra N, Li Z, Chen L, Li B, Zhang X, Wang C, et al. SirT1 is an inhibitor of proliferation and tumor formation in colon cancer. J Biol Chem. 2009;284(27):18210-18217.