Overexpression of SIRT1 is Associated With Poor Outcomes in Patients With Ovarian Carcinoma
Autor: | Shotaro Higuchi, Tanri Shiozawa, Koichi Ida, Yasushi Yamada, Hiroyasu Kashima, Tsutomu Miyamoto, David Hamisi Mvunta, Ryoichi Asaka, Hirofumi Ando |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Histology endocrine system diseases Serous carcinoma Endometriosis Pathology and Forensic Medicine Metastasis 03 medical and health sciences 0302 clinical medicine Sirtuin 1 Ovarian carcinoma medicine Carcinoma Humans Ovarian Neoplasms biology Middle Aged medicine.disease female genital diseases and pregnancy complications Medical Laboratory Technology Serous fluid Treatment Outcome 030104 developmental biology 030220 oncology & carcinogenesis Cancer research biology.protein Female Clear cell |
Zdroj: | Applied Immunohistochemistry & Molecular Morphology. 25:415-421 |
ISSN: | 1541-2016 |
DOI: | 10.1097/pai.0000000000000316 |
Popis: | Sirtuin 1 (SIRT1), originally identified as a longevity gene, regulates DNA repair and metabolism by deacetylating target proteins such as p53. SIRT1 plays a key role in the pathophysiology of metabolic diseases and neurodegenerative disorders, and is considered to protect against age-related diseases including cancer. In contrast, SIRT1 may be oncogenic because its overexpression has been detected in many cancers. The aim of the present study was to clarify the expression and the role of SIRT1 in ovarian carcinoma (OvCa). The expression of SIRT1 was evaluated immunohistochemically in 16 cases of normal ovaries, 35 cases of endometriosis with/without carcinoma, and 68 cases of OvCa (endometrioid, 16; clear cell, 20; mucinous, 16; serous, 16). Staining results were evaluated semiquantitatively by the Immunoreactive Scoring System, and the relationships with clinicopathologic features and outcomes of patients were analyzed. The expression of SIRT1 was higher in endometrioid, mucinous, and clear-cell carcinomas than in the inclusion cysts of normal ovaries, but not in serous carcinoma (P=0.038). The expression of SIRT1 on OvCa did not correlate with age, stage, location of metastasis, or capsular penetration. However, elevated SIRT1 expression was a significant predictor of shorter survival in univariate (P=0.038) and multivariate (P=0.037) survival analyses, regardless of the tumor stage. Results of the present study suggest a positive role for SIRT1 in the development of OvCa and its potential as a novel therapeutic target. |
Databáze: | OpenAIRE |
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