Significance of USP7 in Predicting Prognosis of Mammary Ductal Adenocarcinoma in the Turkish Population

Abstract

Objective: Breast cancer has the highest incidence and mortality rate among women worldwide. This study aims to analyze ubiquitin specific protease 7 (USP7) levels in mammary ductal adenocarcinoma patients in the Turkish population, to identify whether there is a relationship between the levels of USP7 protein and bad prognosis, which is indicated by enlarged tumor size, younger age, and receiving neo-adjuvant treatment. Materials and Methods: In our study, we analyzed USP7 levels by immunohistochemistry (IHC) staining in 38 mammary adenocarcinoma cases in the Turkish population. Corelation analyses were performed to evaluate the distribution of the patients by their age, tumor size, Ki-67 levels, and the status of neo-adjuvant treatment by their USP7 levels. The IHC data concluded that the average age and tumor size are reversely proportional to the USP7 levels, insignificantly. The differences between the levels of USP7 and Ki-67 measurements were found to be statistically insignificant between the groups. Results: Women who received the neo-adjuvant therapy prior to the operation presented much lower amount of USP7 levels when compared to their non-treated counterparts. Conclusions: These findings highlighted that mammary ductal adenocarcinoma patients in the Turkish population present varying USP7 protein levels. Even though the levels of UPS7 are partially insignificant, the presence of USP7 protein might be a prognostic indicator in breast cancer patients in the Turkish population with a larger study set

Keywords

• Ubiquitination
• USP7
• mammary ductal adenocarcinoma
• the Turkish population

References

1. 1. Arnold M, Morgan E, Rumgay H, Mafra A, Singh D, Laversanne M, et al. Current and future burden of breast cancer: Global statistics for 2020 and 2040. The Breast. 2022; 66: 15-23. [CrossRef] google scholar
2. 2. Ellington TD, Miller JW, Henley SJ, Wilson RJ, Wu M, Richardson LC. Trends in breast cancer incidence, by race, ethnicity, and age among women aged >20 years - United States, 1999-2018. MMWR Morb Mortal Wkly Rep 2022; 71(2): 43-7. [CrossRef] google scholar
3. 3. Llewellyn A, Howard C, McCabe C. An exploration of the experiences of women treated with radiotherapy for breast cancer: Learning from recent and historical cohorts to identify enduring needs. Eur J Oncol Nurs 2019; 39; 47-54 [CrossRef] google scholar
4. 4. Global Burden of Disease Cancer Collaboration; Fitzmaurice C, Akinyemiju TF, Al Lami FH, Alam T, Alizadeh-Navaei R, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-Adjusted life-years for 29 cancer groups, 1990 to 2017: A systematic analysis for the global burden of disease study. JAMA Oncol 2018; 4(11): 1553-68. google scholar
5. 5. Al-Mahmood S, Sapiezynski J, Garbuzenko OB, Minko T. Metastatic and triple-negative breast cancer: challenges and treatment options. Drug Deliv Transl Res 2018; 8(5): 1483-507. [CrossRef] google scholar
6. 6. Seçer İ. Spss ve Lisrel ile pratik veri analizi. 2. baskı. Ankara: Anı Yayıncılık; 2015. google scholar
7. 7. Everett RD, Meredith M, Orr A, Cross A, Kathoria M, Parkinson J. A novel ubiquitin-specific protease is dynamically associated with the PML nuclear domain and binds to a herpesvirus regulatory protein. EMBO J 1997; 16(7): 1519-30. [CrossRef] google scholar
8. 8. Li M, Chen D, Shiloh A, Luo J, Nikolaev AY, Qin J, et al. Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization. Nature 2002; 416(6881): 648-53. [CrossRef] google scholar

9. 9. Li M, Brooks CL, Kon N, Gu W. A dynamic role of HAUSP in the p53-Mdm2 pathway. Mol Cell 2004; 13(6): 879-86. [CrossRef] google scholar
10. 10. Lin Y-T, Lin J, Liu Y-E, Chen Y-C, Liu S-T, Hsu K-W, et al. USP7 induces chemoresistance in triple-negative breast cancer via deubiquitination and stabilization of ABCB1. Cells 2022; 11(20): 3294 [CrossRef] google scholar
11. 11. He Y, Zhong Y, Wang Y, Mao X. Recent insights into USP7: Construct, pathophysiology, and inhibitors. GPD 2022; 1(2): 118. [CrossRef] google scholar
12. 12. Zhang L, Wang H, Tian L, Li H. Expression of USP7 and MARCH7 Is correlated with poor prognosis in epithelial ovarian cancer. Tohoku J Exp Med 2016; 239(3): 165-75. [CrossRef] google scholar
13. 13. Zhang M-J, Chen D-S, Li H, Liu W-W, Han G-Y, Han Y-F. Clinical significance of USP7 and EZH2 in predicting prognosis of laryngeal squamous cell carcinoma and their possible functional mechanism. Int J Clin Exp Pathol 2019; 12(6): 2184-94. google scholar
14. 14. Assi HA, Khoury KE, Dbouk H, Khalil LE, Mouhieddine TH, El Saghir NS. Epidemiology and prognosis of breast cancer in young women. J Thorac Dis 2013; 5 Suppl 1(Suppl 1): S2-8. google scholar
15. 15. Giovinazzi S, Morozov VM, Summers MK, Reinhold WC, Ishov AM. USP7 and Daxx regulate mitosis progression and taxane sensitivity by affecting stability of Aurora-A kinase. Cell Death Differ 2013; 20(5): 721-31. [CrossRef] google scholar
16. 16. Cartel M, Mouchel P-L, Gotanègre M, David L, Bertoli S, Mansat-De Mas V, et al. Inhibition of ubiquitin-specific protease 7 sensitizes acute myeloid leukemia to chemotherapy. Leukemia 2021; 35(2): 417-32. [CrossRef] google scholar