Expression of SIRT1 and DBC1 is Associated with Poor Prognosis of Soft Tissue Sarcomas

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Sep 11

PMID 24019980

Citations 36

Authors

Jung Ryul Kim

Young Jae Moon

Keun Sang Kwon

Jun Sang Bae

Sajeev Wagle

Taek Kyun Yu

Kyoung Min Kim

Ho Sung Park

Ju-Hyung Lee

Woo Sung Moon

Ho Lee

Myoung Ja Chung

Kyu Yun Jang

Affiliations

Soon will be listed here.

Abstract

Unlabelled: Recently, the roles of SIRT1 and deleted in breast cancer 1 (DBC1) in human cancer have been extensively studied and it has been demonstrated that they are involved in many human carcinomas. However, their clinical significance for soft-tissue sarcomas has not been examined. In this study, we evaluated the expression and prognostic significance of the expression of SIRT1, DBC1, P53, β-catenin, cyclin D1, and KI67 in 104 cases of soft-tissue sarcomas.

Results: Immunohistochemical expression of SIRT1, DBC1, P53, β-catenin, and cyclin D1 were seen in 71%, 74%, 53%, 48%, and 73% of sarcomas, respectively. The expression of SIRT1, DBC1, P53, β-catenin, and cyclin D1 were significantly correlated with advanced clinicopathological parameters such as higher clinical stage, higher histological grade, increased mitotic counts, and distant metastasis. The expression of SIRT1, DBC1, P53, β-catenin, cyclin D1, and KI67 were significantly correlated with each other and positive expression of all of these predicted shorter overall survival and event-free survival by univariate analysis. Multivariate analysis revealed the expression of SIRT1 as an independent prognostic indicator for overall survival and event-free survival of sarcoma patients. In conclusion, this study demonstrates that SIRT1- and DBC1-related pathways may be involved in the progression of soft-tissue sarcomas and can be used as clinically significant prognostic indicators for sarcoma patients. Moreover, the SIRT1- and DBC1-related pathways could be new therapeutic targets for the treatment of sarcomas.

Citing Articles

Mechanistic insights into the dual role of CCAR2/DBC1 in cancer.

Kim H, Moon S, Kim J Exp Mol Med. 2023; 55(8):1691-1701.

PMID: 37524873 PMC: 10474295. DOI: 10.1038/s12276-023-01058-1.

Sirtuins (SIRTs) As a Novel Target in Gastric Cancer.

Poniewierska-Baran A, Warias P, Zgutka K Int J Mol Sci. 2022; 23(23).

PMID: 36499440 PMC: 9737976. DOI: 10.3390/ijms232315119.

Recent advances of SIRT1 and implications in chemotherapeutics resistance in cancer.

Yousafzai N, Jin H, Ullah M, Wang X Am J Cancer Res. 2021; 11(11):5233-5248.

PMID: 34873458 PMC: 8640807.

Expression Patterns of TOP2A and SIRT1 Are Predictive of Survival in Patients with High-Risk Soft Tissue Sarcomas Treated with a Neoadjuvant Anthracycline-Based Chemotherapy.

Berclaz L, Altendorf-Hofmann A, Durr H, Klein A, Angele M, Albertsmeier M Cancers (Basel). 2021; 13(19).

PMID: 34638362 PMC: 8507907. DOI: 10.3390/cancers13194877.

CCAR1 and CCAR2 as gene chameleons with antagonistic duality: Preclinical, human translational, and mechanistic basis.

Johnson G, Rajendran P, Dashwood R Cancer Sci. 2021; 111(10):3416-3425.

PMID: 33403784 PMC: 7540973. DOI: 10.1111/cas.14579.

References

Marshall G, Gherardi S, Xu N, Neiron Z, Trahair T, Scarlett C . Transcriptional upregulation of histone deacetylase 2 promotes Myc-induced oncogenic effects. Oncogene. 2010; 29(44):5957-68. DOI: 10.1038/onc.2010.332. View

Alhazzazi T, Kamarajan P, Verdin E, Kapila Y . SIRT3 and cancer: tumor promoter or suppressor?. Biochim Biophys Acta. 2011; 1816(1):80-8. PMC: 3129516. DOI: 10.1016/j.bbcan.2011.04.004. View

Chen W, Wang D, Yen R, Luo J, Gu W, Baylin S . Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses. Cell. 2005; 123(3):437-48. DOI: 10.1016/j.cell.2005.08.011. View

Lara E, Mai A, Calvanese V, Altucci L, Lopez-Nieva P, Martinez-Chantar M . Salermide, a Sirtuin inhibitor with a strong cancer-specific proapoptotic effect. Oncogene. 2008; 28(6):781-91. DOI: 10.1038/onc.2008.436. View

Imai S, ARMSTRONG C, Kaeberlein M, Guarente L . Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000; 403(6771):795-800. DOI: 10.1038/35001622. View

Peck B, Chen C, Ho K, Di Fruscia P, Myatt S, Coombes R . SIRT inhibitors induce cell death and p53 acetylation through targeting both SIRT1 and SIRT2. Mol Cancer Ther. 2010; 9(4):844-55. DOI: 10.1158/1535-7163.MCT-09-0971. View

Wong C, Fan S, Ng I . beta-Catenin mutation and overexpression in hepatocellular carcinoma: clinicopathologic and prognostic significance. Cancer. 2001; 92(1):136-45. DOI: 10.1002/1097-0142(20010701)92:1<136::aid-cncr1301>3.0.co;2-r. View

Li Z, Chen L, Kabra N, Wang C, Fang J, Chen J . Inhibition of SUV39H1 methyltransferase activity by DBC1. J Biol Chem. 2009; 284(16):10361-6. PMC: 2667723. DOI: 10.1074/jbc.M900956200. View

Jang K, Noh S, Lehwald N, Tao G, Bellovin D, Park H . SIRT1 and c-Myc promote liver tumor cell survival and predict poor survival of human hepatocellular carcinomas. PLoS One. 2012; 7(9):e45119. PMC: 3443243. DOI: 10.1371/journal.pone.0045119. View

10.

Mao B, Zhao G, Lv X, Chen H, Xue Z, Yang B . Sirt1 deacetylates c-Myc and promotes c-Myc/Max association. Int J Biochem Cell Biol. 2011; 43(11):1573-81. DOI: 10.1016/j.biocel.2011.07.006. View

11.

Liang X, Finkel T, Shen D, Yin J, Aszalos A, Gottesman M . SIRT1 contributes in part to cisplatin resistance in cancer cells by altering mitochondrial metabolism. Mol Cancer Res. 2008; 6(9):1499-506. PMC: 2597364. DOI: 10.1158/1541-7786.MCR-07-2130. View

12.

Dickson B, Riddle N, Brooks J, Pasha T, Zhang P . Sirtuin 1 (SIRT1): a potential immunohistochemical marker and therapeutic target in soft tissue neoplasms with myoid differentiation. Hum Pathol. 2013; 44(6):1125-30. DOI: 10.1016/j.humpath.2012.10.001. View

13.

Liu T, Liu P, Marshall G . The critical role of the class III histone deacetylase SIRT1 in cancer. Cancer Res. 2009; 69(5):1702-5. DOI: 10.1158/0008-5472.CAN-08-3365. View

14.

Kim S, Kim J, Yu E, Lee K, Park C . The overexpression of DBC1 in esophageal squamous cell carcinoma correlates with poor prognosis. Histol Histopathol. 2011; 27(1):49-58. DOI: 10.14670/HH-27.49. View

15.

Kang H, Jung J, Kim M, Chung J . CK2 is the regulator of SIRT1 substrate-binding affinity, deacetylase activity and cellular response to DNA-damage. PLoS One. 2009; 4(8):e6611. PMC: 2721681. DOI: 10.1371/journal.pone.0006611. View

16.

Bae H, Chang Y, Noh J, Kim J, Eun J, Jung K . DBC1 does not function as a negative regulator of SIRT1 in liver cancer. Oncol Lett. 2012; 4(5):873-877. PMC: 3499483. DOI: 10.3892/ol.2012.875. View

17.

Allred D, Harvey J, Berardo M, Clark G . Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998; 11(2):155-68. View

18.

Hoos A, Stojadinovic A, Mastorides S, URIST M, Polsky D, Di Como C . High Ki-67 proliferative index predicts disease specific survival in patients with high-risk soft tissue sarcomas. Cancer. 2001; 92(4):869-74. DOI: 10.1002/1097-0142(20010815)92:4<869::aid-cncr1395>3.0.co;2-u. View

19.

Engellau J, Bendahl P, Persson A, Domanski H, Akerman M, Gustafson P . Improved prognostication in soft tissue sarcoma: independent information from vascular invasion, necrosis, growth pattern, and immunostaining using whole-tumor sections and tissue microarrays. Hum Pathol. 2005; 36(9):994-1002. DOI: 10.1016/j.humpath.2005.07.008. View

20.

Lehwald N, Tao G, Jang K, Sorkin M, Knoefel W, Sylvester K . Wnt-β-catenin signaling protects against hepatic ischemia and reperfusion injury in mice. Gastroenterology. 2011; 141(2):707-18, 718.e1-5. PMC: 4084974. DOI: 10.1053/j.gastro.2011.04.051. View