Prognostic and Clinicopathological Value of SIRT1 Expression in Female Reproductive System Cancer

Author(s): Shuai Zhang, Zhe Sun, Yuewen Qi, Xiaolu Fang, Hong Yu

Objective: Numerous epidemiological studies have reported the association between silent mating type information regulation 2 homolog-1 (SIRT1) and female reproductive system cancer, but the data of different reports remains controversial. To accurately evaluate the significance of SIRT1 expression in reproductive system cancer, a meta-analysis based on published studies was conducted. Methods: Relevant articles before August 2017 on SIRT1 and reproductive system cancer were searched via PubMed, Embase, Cochrane Central and Chinese National Knowledge Infrastructure databases(NCBI). The studies were chosen for the meta-analysis based on requisite criteria. The overall survival (OS) and clinical features including FIGO stage , lymph node metastasis (LNM) and tumor grade were analyzed using RevMan 5.3 software. Odds ratios (OR) , hazard ratios (HR) and their 95% corresponding confidence intervals (CI) were pooled to estimate the effect of specific associations. Results: A total of 14 eligible studies containing 1002 patients were enrolled, in which 47.9% of the patients overexpressed SIRT1. The results showed that SIRT1 overexpression significantly correlated with the risk of reproductive cancers (OR=3.92, 95% CI: 3.06–5.02, P<0.00001), histological grade (OR=2.47, 95% CI=1.19-5.13, p=0.02), LNM (OR=3.25, 95% CI=1.85-5.70, P<0.0001), but no statistical significance was related to FIGO stage (OR=1.84, 95% CI=1.00-3037, P=0.05) and overall survival (HR=1.32, 95% CI=1.00-1.75, P=0.05) of female reproductive system cancer. Conclusions: The overall data of the shown meta-analysis suggested that the expression of SIRT1 is correlated with cancer risk, lymph node metastasis and histological grade. However, the over-expression of SIRT1 have no statistical significance with FIGO stage and overall survival.

SIRT1, Reproductive System Cancer, Clinicopathological Characteristics, Prognosis, Meta-Analysis

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011; 61: 69-90. doi: 10.3322/caac.20107. caac.20107.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016; 66:7-30.
3. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, ebelo M, Parkin DM, Forman D, Bray, F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 29/ December/2015.
4. Shen H, Laird PW. Interplay between the cancer genome and epigenome. Cell. 2013; 153:38–55. doi: 10.1016/j. cell.2013.03.008.
5. Yuan H, Su L, Wen Y C. The emerging and diverse roles of sirtuins in cancer: a clinical perspective[J]. Oncotargets & Therapy, 2013, 6(default):1399-1416.
6. Imai S, Armstrong CM, Kaeberlein M and Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 2000; 403: 795-800
7. Cantó C, Auwerx J. Interference between PARPs and SIRT1: a novel approach to healthy ageing?[J]. Aging, 2011, 3(5):543.
8. Leibiger I B, Berggren P O. Sirt1: a metabolic master switch that modulates lifespan[J]. Nature Medicine, 2006, 12(1):34.
9. Zhang W, Wu H, Yang M, et al. SIRT1 inhibition impairs non-homologous end joining DNA damage repair by increasing Ku70 acetylation in chronic myeloid leukemia cells[J]. Oncotarget, 2016, 7(12):13538-13550.
10. Lee H, Kim K R, Noh S J, et al. Expression of DBC1 and SIRT1 is associated with poor prognosis for breast carcinoma.[J]. Human Pathology, 2011, 42(2):204-213. Wu Y, Meng X, Huang C, et al. Emerging role of silent information regulator 1 (SIRT1) in hepatocellular carcinoma: a potential therapeutic target.[J]. Tumor Biology, 2015, 36(6):4063-4074.
11. Li Y, Xu S, Jing L, et al. SIRT1 facilitates hepatocellular carcinoma metastasis by promoting PGC-1α-mediated mitochondrial biogenesis[J]. Oncotarget, 2016, 7(20):29255-29274.
12. Grbesa I, Pajares M J, Martínez-Terroba E, et al. Expression of sirtuin 1 and 2 is associated with poor prognosis in non-small cell lung cancer patients[J]. Plos One, 2015, 10(4):e0124670.
13. Zhao G, Cui J, Zhang J G, et al. SIRT1 RNAi knockdown induces apoptosis and senescence, inhibits invasion and enhances chemosensitivity in pancreatic cancer cells[J]. Gene Therapy, 2011, 18(9):920-8.
14. Yang Q, Wang B, Gao W, et al. SIRT1 is downregulated in gastric cancer and leads to G1-phase arrest via NF-κB/Cyclin D1 signaling[J]. Molecular Cancer Research Mcr, 2013, 11(12):1497.
15. Wang, RuiHong, Zheng, et al. Interplay among BRCA1, SIRT1, and Survivin during BRCA1-Associated Tumorigenesis[J]. Molecular Cell, 2008, 32(1):11-20.
16. Teramae M, Fukuda T, Wada T, et al. Sirtuin1 expression predicts the efficacy of neoadjuvant chemotherapy for locally advanced uterine cervical cancer.[J]. Molecular & Clinical Oncology, 2015, 3(1):73-78.
17. Singh S, Kumar P U, Thakur S, et al. Expression/localization patterns of sirtuins (SIRT1, SIRT2, and SIRT7) during progression of cervical cancer and effects of sirtuin inhibitors on growth of cervical cancer cells[J]. Tumour Biology the Journal of the International Society for Oncodevelopmental Biology & Medicine, 2015, 36(8):6159-6171.
18. Asaka R, Miyamoto T, Yamada Y, et al. Sirtuin 1 promotes the growth and cisplatin resistance of endometrial carcinoma cells: a novel therapeutic target[J]. Laboratory investigation; a journal of technical methods and pathology, 2015, 95(12):1363.
19. Carla B, Sara M R, Diogo A R, et al. Assessing sirtuin expression in endometrial carcinoma and non-neoplastic endometrium:[J]. Oncotarget, 2016, 7(2):1144-1154.
20. Li lin. SIRT1 expression in endometrioid carcinoma and the influence and mechanism of SIRT1 on the biological behavior of endometrial ancer cells [D]. Shandong university, 2015.
21. Guo H Y, Zhang Y L, Zhi-Hong LI, et al. Expression and significance of SIRT1 and Survivin in endometrial carcinoma[J]. Chinese Journal of Clinical & Experimental Pathology, 2012.
22. Wei L ,Wang R, Guan S. The expression and significance of ILK, SIRT1 and PTEN in endometrial carcinoma of endometrium [J]. Chinese women and children health, 2014, 29 (29) : 4747-4749.
23. Dong H S, Choi Y J, Peng J, et al. Distinct effects of SIRT1 in cancer and stromal cells on tumor promotion[J]. Oncotarget, 2016, (17):23975-23987.
24. Shuang T, Wan M, Zhou Y, et al. Over-expression of Sirt1 contributes to chemoresistance and indicates poor prognosis in serous epithelial ovarian cancer (EOC)[J]. Medical Oncology, 2015, 32(12):260.
25. Mvunta D H, Miyamoto T, Asaka R, et al. Overexpression of SIRT1 is Associated With Poor Outcomes in Patients With Ovarian Carcinoma.[J]. Appl Immunohistochem Mol Morphol, 2016:1.
26. Jang K Y, Kim K S, Hwang S H, et al. Expression and prognostic significance of SIRT1 in ovarian epithelial tumours[J]. Pathology, 2009, 41(4):366-371.
27. Zhao Q S. Prognostic significance of acetylated TP53k382 and SIRT1
28. expression by human ovarian carcinoma [D]. luzhou medical university , 2013.
29. Zheng X M, Lin Y F, lu Z, et al. Expression of P53, CyclinB1 and SIRT1 in Serous Ovarian Neoplasm Tissue and Their Relationships with Clinicopathological Features [J]. Tumor pharmacology, 2017, 7 (1) : 69-73.
30. Shi G, Bi F F, Yang Q. The expression and significance of BRCA1 and SIRT1 in serous epithelial ovarian cancer [J]. Modern oncology medicine, 2017, 25 (11) : 1777-1779.
31. Wang C, Yang W, Dong F, et al. The prognostic role of Sirt1 expression in solid malignancies: a meta-analysis.[J]. Oncotarget, 2017.
32. Hisahara S, Chiba S, Matsumoto H, et al. Histone Deacetylase SIRT1 Modulates Neuronal Differentiation by Its Nuclear Translocation[J]. Proceedings of the National Academy of Sciences of the United States of America, 2008, 105(40):15599-15604.