Background: Salivary gland tumors (SGTs) include benign and malignant tumors, such as pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC). Baculoviral inhibitors of apoptotic proteins (BIAPs) repeat-containing protein 6 (BIRC6), is an anti-apoptotic protein that plays an important role in cancers. Purpose: We aimed to evaluate the expression of BIRC6 in SGTs and its correlation with the clinicopathological features. Materials and Method: In this cross-sectional study, 56 SGT tissue samples, including 15 cases of MEC, 20 cases of ACC, and 21 cases of PA, as well as nine cases of normal salivary gland tissues, were investigated for BIRC6 expression by immunohistochemical analysis. Results: BIRC6 was found in 2.50%, 63%, 88%, and 63% of normal tissue, MEC, ACC, and PA, respectively. The mean total score of BIRC6 expression was 9.13; for ACC, MEC, PA, and normal tissue of the salivary gland were 10.25, 9.13, 9.00, and 3.00, respectively. The high expression of BIRC6 was detected in 29 cases of malignant and 15 cases of benign SGTs. The frequency of high or low expression was not different between the male and female patients (p= 0.833), patients aged below or above 65 years (p= 0.950), patients with different tumor sizes (p= 0.734), and metastasis status (p= 0.977). Conclusion: The higher expression intensity and percentage of BIRC6 in malignant and benign SGTs suggests it as a potential marker to be used in future targeted therapy for SGTs. |
- Sentani K, Ogawa I, Ozasa K, Sadakane A, Utada M, Tsuya T, et al. Characteristics of 5015 salivary gland neoplasms registered in the Hiroshima tumor tissue registry over a period of 39 years. J Clin Med. 2019; 8: 566.
- Wilson KF, Meier JD, Ward PD. Salivary gland disorders. Am Fam Physic. 2014; 89: 882-888.
- Seethala RR. Salivary gland tumors: current concepts and controversies. Surg Pathol Clin. 2017; 10: 155-176.
- Board PATE. Salivary Gland Cancer Treatment (Adult) (PDQ®). PDQ Cancer Information Summaries. Availablat at: https://www.cancer.gov/types/head-and-neck/hp/adult/salivary-gland-treatment-pdq
- Guzzo M, Locati LD, Prott FJ, Gatta G, McGurk M, Licitra L. Major and minor salivary gland tumors. Crit Rev Oncol Hematol. 2010; 74: 134-148.
- Nagao T, Sato E, Inoue R, Oshiro H, Takahashi RH, Nagai T, et al. Immunohistochemical analysis of salivary gland tumors: application for surgical pathology practice. Acta Histochem Cytochem. 2012; 45: 269-282.
- Xu B, Haroon*Al*Rasheed MR, Antonescu CR, Alex D, Frosina D, Ghossein R, et al. Pan‐Trk immunohistochemistry is a sensitive and specific ancillary tool in diagnosing secretory carcinoma of salivary gland and detecting ETV 6‐NTRK 3 fusion. Histopathology. 2020; 76: 375-382.
- Saleem M, Qadir MI, Perveen N, Ahmad B, Saleem U, Irshad T, et al. Inhibitors of apoptotic proteins: new targets for anticancer therapy. Chem Biol Drug Des. 2013; 82: 243-251.
- Dong X, Lin D, Low C, Vucic EA, English JC, Yee J, et al. Elevated expression of BIRC6 protein in non–small-cell lung cancers is associated with cancer recurrence and chemoresistance. J Thorac Oncol. 2013; 8: 161-170.
- Wang L, Chen YJ, Hou J, Wang YY, Tang WQ, Shen XZ, et al. Expression and clinical significance of BIRC6 in human epithelial ovarian cancer. Tumour Biol. 2014; 35: 4891-4896.
- Hu T, Weng S, Tang W, Xue R, Chen S, Cai G, et al. Overexpression of BIRC6 is a predictor of prognosis for colorectal cancer. PLoS One. 2015; 10: e0125281.
- Luk SUI, Xue H, Cheng H, Lin D, Gout PW, Fazli L, et al. The BIRC6 gene as a novel target for therapy of prostate cancer: dual targeting of inhibitors of apoptosis. Oncotarget. 2014; 5: 6896.
- Lu M, Zhan X. The crucial role of multiomic approach in cancer research and clinically relevant outcomes. EPMA J. 2018; 9: 77-102.
- Matse JH, Yoshizawa J, Wang X, Elashoff D, Bolscher JG, Veerman EC, et al. Discovery and prevalidation of salivary extracellular microRNA biomarkers panel for the noninvasive detection of benign and malignant parotid gland tumors. Clin Cancer Res. 2013; 19: 3032-3038.
- Seethala RR. Histologic grading and prognostic biomarkers in salivary gland carcinomas. Adv Anat Pathol. 2011; 18: 29-45.
- Stenman G, Persson F, Andersson MK. Diagnostic and therapeutic implications of new molecular biomarkers in salivary gland cancers. Oral Oncol. 2014; 50: 683-690.
- Schnoell J, Kadletz L, Jank BJ, Oberndorfer F, Brkic FF, Gurnhofer E, et al. Expression of inhibitors of apoptosis proteins in salivary gland adenoid cystic carcinoma: XIAP is an independent marker of impaired cause specific survival. Clin Otolaryngol. 2020; 45: 364-369.
- Cancer Net Editorial Board. Salivary Gland Cancer: Stages and Grades. [Cited:25/12]. Available at: https://www.cancer.net/cancer-types/salivary-gland-cancer/stages-and-grades.
- Prisco MG, Zannoni GF, De*Stefano I, Vellone VG, Tortorella L, Fagotti A, et al. Prognostic role of metastasis tumor antigen 1 in patients with ovarian cancer: a clinical study. Hum Pathol. 2012; 43: 282-288.
- Jan R. Understanding apoptosis and apoptotic pathways targeted cancer therapeutics. Adv Pharm Bull. 2019; 9: 205-218.
- Lamers F, Schild L, Koster J, Speleman F, Øra I, Westerhout EM, et al. Identification of BIRC6 as a novel intervention target for neuroblastoma therapy. BMC Cancer. 2012; 12: 285.
- Gómez*Bergna SM, Marchesini A, Amorós*Morales LC, Arrías PN, Farina HG, Romanowski V, et al. Exploring the Role of the Inhibitor of Apoptosis BIRC6 in Breast Cancer: A Database Analysis. JCO Clin Cancer Inform. 2022; 6: e2200093.
- Derakhshan A, Chen Z, Van*Waes C. Therapeutic small molecules target inhibitor of apoptosis proteins in cancers with deregulation of extrinsic and intrinsic cell death pathways. Clin Cancer Res. 2017; 23: 1379-1387.
- Cetraro P, Plaza-Diaz J, MacKenzie A, Abadía-Molina F. A review of the current impact of inhibitors of apoptosis proteins and their repression in cancer. Cancers. 2022; 14: 1671.
- Low CG, Luk IS, Lin D, Fazli L, Yang K, Xu Y, et al. BIRC6 protein, an inhibitor of apoptosis: role in survival of human prostate cancer cells. PLoS One. 2013; 8: e55837.
- Van*Houdt WJ, Emmink BL, Pham TV, Piersma SR, Verheem A, Vries R, et al. Comparative proteomics of colon cancer stem cells and differentiated tumor cells identifies BIRC6 as a potential therapeutic target. Mol Cell Proteomics. 2011; 10: M111.011353.
- Li R, Chen BL, Zhou YW, Guo RW, Shuai MT, Zeng JX, et al. Expression and clinical significance of Apollon in esophageal squamous cell carcinoma. Mol Med Rep. 2016; 14: 1933-1940.
- Gharabaghi MA. Diagnostic investigation of BIRC 6 and SIRT 1 protein expression level as potential prognostic biomarkers in patients with non‐small cell lung cancer. Clin Respir J. 2018; 12: 633-638.
- Eskandari F, Razavian A, Zare R, Ejlali S, Razmahang A, Zanjani M, et al. Evaluation of BIRC6 Expression in Oral Squamous Cell Carcinoma, Epithelial Dysplasia, Lichen Planus with and without Dysplasia, and Hyperkeratosis. Diagnostics. 2023; 13: 3560.
- Guo H, Zhong W, Wang X, Pan B, Li F, Lu K, et al. Expression and clinical significance of Apollon in renal carcinoma. Oncol Lett. 2016; 12: 5129-5135.
- Schläfli AM, Torbett BE, Fey MF, Tschan MP. BIRC6 (APOLLON) is down-regulated in acute myeloid leukemia and its knockdown attenuates neutrophil differentiation. Exp Hematol Oncol. 2012; 1: 25.
- Zhuang W, Zhang C, Hao F, Sun X. Baculoviral IAP repeat containing 6 (BIRC6) is a predictor of prognosis in prostate cancer. Med Sci Monit. 2018; 24: 839-845.
- Liu J, Lu Y, Huang W, He Z. Comprehensive Analysis of Inhibitor of Apoptosis Protein Expression and Prognostic Significance in Non–Small Cell Lung Cancer. Front Genet. 2021; 12: 764270.
- Banakar M, Ardekani ST, Zare R, Malekzadeh M, Mirhadi H, Khademi B, et al. Oral squamous cell carcinoma: the role of BIRC6 serum level. Biomed Res Int. 2022; 2022: 5425478.
- Low CGM. The role of BIRC6, a member of the inhibitor of apoptosis protein (IAP) family, in the survival of human prostate cancer cells: University of British Columbia; 2010. Available at: https://open.library.ubc.ca/soa/ cIRcle/collections/ubctheses/24/items/1.0071420
- Ismail EAR, Mahmoud HM, Tawfik LM, Habashy DM, Adly AAM, El‐Sherif NH, et al. BIRC6/Apollon gene expression in childhood acute leukemia: impact on therapeutic response and prognosis. Eur J Haematol. 2012; 88: 118-127.
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