Seong Uk Jeh1, Jung Je Park2, Jong Sil Lee3, Dong Chul Kim3, Jungmo Do1, Sin Woo Lee1, See Min Choi1, Jae Seog Hyun1, Deok Ha Seo1, Chunwoo Lee4, Sung Chul Kam4, Ky Hyun Chung4, Jeong Seok Hwa5. 1. Department of Urology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Republic of Korea. 2. Department of Otorhinolaryngology and Pathology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Republic of Korea. Electronic address: capetown@hanmail.net. 3. Department of Otorhinolaryngology and Pathology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Republic of Korea. 4. Department of Urology, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea. 5. Department of Urology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Republic of Korea. Electronic address: seogee@gnu.ac.kr.
Abstract
OBJECTIVES: Sirtuins (1-7) are evolutionarily conserved NAD-dependent deacetylases that play an important role in carcinogenesis. However, their role in renal cell carcinoma (RCC) remains unclear. The objective of the present study was to examine the role of SIRTs in RCC carcinogenesis and prognosis. MATERIALS AND METHODS: Paraffin-embedded specimens from 102 patients who underwent extirpative renal surgeries for renal masses between January 2004 and December 2010 were examined. SIRT expression was compared between RCC and adjacent normal kidney tissues by immunohistochemical staining. Survival differences and cancer-specific survival were analyzed with the Kaplan-Meier log-rank test and univariate and multivariate Cox regression analyses, respectively. RESULTS: SIRT1, SIRT3, and SIRT6 expression was significantly lower in RCC than in normal tissues (P = 0.001, P = 0.006, and P = 0.033, respectively), whereas the expression of other SIRT proteins did not differ significantly between the 2 tissues. SIRT3 expression was significantly associated with longer cancer-specific survival (HR = 0.133, P = 0.047), after adjusting for age, T stage, Fuhrman grade, Karnofsky performance status, and distant metastases. Kaplan-Meier analysis showed that patients with high-SIRT3 expression had relatively better survival than those with low-SIRT3 expression (P = 0.046, log-rank test). CONCLUSIONS: Our results provide preliminary evidence suggesting that SIRT1, SIRT3, and SIRT6 function as tumor suppressors in RCC. In particular, SIRT3 seems to have a favorable influence on the survival of patients with clear cell RCC.
OBJECTIVES: Sirtuins (1-7) are evolutionarily conserved NAD-dependent deacetylases that play an important role in carcinogenesis. However, their role in renal cell carcinoma (RCC) remains unclear. The objective of the present study was to examine the role of SIRTs in RCC carcinogenesis and prognosis. MATERIALS AND METHODS:Paraffin-embedded specimens from 102 patients who underwent extirpative renal surgeries for renal masses between January 2004 and December 2010 were examined. SIRT expression was compared between RCC and adjacent normal kidney tissues by immunohistochemical staining. Survival differences and cancer-specific survival were analyzed with the Kaplan-Meier log-rank test and univariate and multivariate Cox regression analyses, respectively. RESULTS:SIRT1, SIRT3, and SIRT6 expression was significantly lower in RCC than in normal tissues (P = 0.001, P = 0.006, and P = 0.033, respectively), whereas the expression of other SIRT proteins did not differ significantly between the 2 tissues. SIRT3 expression was significantly associated with longer cancer-specific survival (HR = 0.133, P = 0.047), after adjusting for age, T stage, Fuhrman grade, Karnofsky performance status, and distant metastases. Kaplan-Meier analysis showed that patients with high-SIRT3 expression had relatively better survival than those with low-SIRT3 expression (P = 0.046, log-rank test). CONCLUSIONS: Our results provide preliminary evidence suggesting that SIRT1, SIRT3, and SIRT6 function as tumor suppressors in RCC. In particular, SIRT3 seems to have a favorable influence on the survival of patients with clear cell RCC.
Authors: Vera Miranda-Gonçalves; Ana Lameirinhas; Catarina Macedo-Silva; João Lobo; Paula C Dias; Verónica Ferreira; Rui Henrique; Carmen Jerónimo Journal: Cells Date: 2020-04-23 Impact factor: 6.600