Prognostic Significance of Sirtuins Expression in Papillary Thyroid Carcinoma
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background and Objectives: Sirtuins (SIRTs) play important roles in cellular and organismal homeostasis. They have distinct gene expression patterns in various cancers; however, the relationship between SIRT expression and the progression of thyroid cancer is unclear. We investigated the expression of SIRTs in patients with papillary thyroid carcinoma (PTC) and their role as biomarkers for predicting the aggressiveness of this disease. Materials and Methods: We used immunohistochemical staining to evaluate the expression of SIRT1 and SIRT3 in tumor specimens from 270 patients with PTC. We also evaluated the potential association between SIRT expression and diverse clinicopathological features. Results: High SIRT1 expression was negatively correlated with lymphovascular invasion, central lymph node metastasis, and lateral lymph node metastasis. Multivariate analyses revealed that high SIRT1 expression was a negative independent risk factor for lateral lymph node metastasis. By contrast, high SIRT3 expression was positively correlated with locoregional recurrence. Interestingly, when patients were grouped by tumor SIRT expression patterns, the group with low SIRT1 expression and high SIRT3 expression was correlated with more aggressive cancer phenotypes including central lymph node metastasis and lateral lymph node metastasis. Conclusion: Our results suggest that SIRTs play dual roles in tumor progression, and the combination of decreased SIRT1 expression and increased SIRT3 expression is significantly associated with a poor prognosis in patients with PTC.
Abstract
Background and Objectives: Sirtuins (SIRTs) play important roles in cellular and organismal homeostasis. They have distinct gene expression patterns in various cancers; however, the relationship between SIRT expression and the progression of thyroid cancer is unclear. We investigated the expression of SIRTs in patients with papillary thyroid carcinoma (PTC) and their role as biomarkers for predicting the aggressiveness of this disease. Materials and Methods: We used immunohistochemical staining to evaluate the expression of SIRT1 and SIRT3 in tumor specimens from 270 patients with PTC. We also evaluated the potential association between SIRT expression and diverse clinicopathological features. Results: High SIRT1 expression was negatively correlated with lymphovascular invasion, central lymph node metastasis, and lateral lymph node metastasis. Multivariate analyses revealed that high SIRT1 expression was a negative independent risk factor for lateral lymph node metastasis. By contrast, high SIRT3 expression was positively correlated with locoregional recurrence. Interestingly, when patients were grouped by tumor SIRT expression patterns, the group with low SIRT1 expression and high SIRT3 expression was correlated with more aggressive cancer phenotypes including central lymph node metastasis and lateral lymph node metastasis. Conclusion: Our results suggest that SIRTs play dual roles in tumor progression, and the combination of decreased SIRT1 expression and increased SIRT3 expression is significantly associated with a poor prognosis in patients with PTC.
참고문헌 (32)
- Guarente L, "Epstein lecture: sirtuins, aging, and medicine", N Engl J Med, 364(23), pp.2235~2244 (2011)
- Frye RA, "Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins", Biochem Biophys Res Commun, 273(2), pp.793~798 (2000)
- Ward PS, "Metabolic reprogramming: a cancer hallmark even warburg did not anticipate", Cancer Cell, 21(3), pp.297~308 (2012)
- Chalkiadaki A, "The multifaceted functions of sirtuins in cancer", Nat Rev Cancer, 15(10), pp.608~624 (2015)
- Hanahan D, "Hallmarks of cancer: the next generation", Cell, 144(5), pp.646~674 (2011)
- Mirebeau-Prunier D, "Estrogen-related receptor alpha modulates lactate dehydrogenase activity in thyroid tumors", PLoS One, 8(3), pp.e58683~ (2013)
- Lee MH, "Mitochondrial localization and regulation of BRAFV600E in thyroid cancer: a clinically used RAF inhibitor is unable to block the mitochondrial activities of BRAFV600E", J Clin Endocrinol Metab, 96(1), pp.E19~E30 (2011)
- Herranz D, "SIRT1 promotes thyroid carcinogenesis driven by PTEN deficiency", Oncogene, 32(34), pp.4052~4056 (2013)
- Kweon KH, "Sirt1 induction confers resistance to etoposide-induced genotoxic apoptosis in thyroid cancers", Int J Oncol, 45(5), pp.2065~2075 (2014)
- Finkel T, "Recent progress in the biology and physiology of sirtuins", Nature, 460(7255), pp.587~591 (2009)
- Pfluger PT, "Sirt1 protects against high-fat diet-induced metabolic damage", Proc Natl Acad Sci U S A, 105(28), pp.9793~9798 (2008)
- Herranz D, "Sirt1 improves healthy ageing and protects from metabolic syndromeassociated cancer", Nat Commun, 1, pp.3~ (2010)
- Fang Y, "Sirtuin 1 in malignant transformation: friend or foe?", Cancer Lett, 306(1), pp.10~14 (2011)
- Deng CX, "SIRT1, is it a tumor promoter or tumor suppressor?", Int J Biol Sci, 5(2), pp.147~152 (2009)
- Huffman DM, "SIRT1 is significantly elevated in mouse and human prostate cancer", Cancer Res, 67(14), pp.6612~6618 (2007)
- Bradbury CA, "Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors", Leukemia, 19(10), pp.1751~1759 (2005)
- Lim CS, "SIRT1: tumor promoter or tumor suppressor?", Med Hypotheses, 67(2), pp.341~344 (2006)
- Banks AS, "SirT1 gain of function increases energy efficiency and prevents diabetes in mice", Cell Metab, 8(4), pp.333~341 (2008)
- Firestein R, "The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth", PLoS One, 3(4), pp.e2020~ (2008)
- Kabra N, "SirT1 is an inhibitor of proliferation and tumor formation in colon cancer", J Biol Chem, 284(27), pp.18210~18217 (2009)
- Wang RH, "Interplay among BRCA1, SIRT1, and Survivin during BRCA1-associated tumorigenesis", Mol Cell, 32(1), pp.11~20 (2008)
- Lombard DB, "Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation", Mol Cell Biol, 27(24), pp.8807~8814 (2007)
- Hirschey MD, "SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation", Nature, 464(7285), pp.121~125 (2010)
- Sundaresan NR, "Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice", J Clin Invest, 119(9), pp.2758~2771 (2009)
- Li S, "p53-induced growth arrest is regulated by the mitochondrial SirT3 deacetylase", PLoS One, 5(5), pp.e10486~ (2010)
- Ashraf N, "Altered sirtuin expression is associated with node-positive breast cancer", Br J Cancer, 95(8), pp.1056~1061 (2006)
- Allison SJ, "SIRT3 is pro-apoptotic and participates in distinct basal apoptotic pathways", Cell Cycle, 6(21), pp.2669~2677 (2007)
- Ford J, "Cancer-specific functions of SIRT1 enable human epithelial cancer cell growth and survival", Cancer Res, 65(22), pp.10457~10463 (2005)
- Bell EL, "The SirT3 divining rod points to oxidative stress", Mol Cell, 42(5), pp.561~568 (2011)
- Hallows WC, "Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction", Mol Cell, 41(2), pp.139~149 (2011)
- Wang RH, "Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice", Cancer Cell, 14(4), pp.312~323 (2008)
- Jang KY, "SIRT1 and c-Myc promote liver tumor cell survival and predict poor survival of human hepatocellular carcinomas", PLoS One, 7(9), pp.e45119~ (2012)
