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Prognostic implications of polycomb proteins ezh2, suz12, and eed1 and histone modification by H3K27me3 in sarcoma.

Authors
 Yong Jin Cho  ;  Soo Hee Kim  ;  Eun Kyung Kim  ;  Jung Woo Han  ;  Kyoo-Ho Shin  ;  Hyuk Hu  ;  Kyung Sik Kim  ;  Young Deuk Choi  ;  Sunghoon Kim  ;  Young Han Lee  ;  Jin-Suck Suh  ;  Joong Bae Ahn  ;  Hyun Cheol Chung  ;  Sung Hoon Noh  ;  Sun Young Rha  ;  Sung-Taek Jung  ;  Hyo Song Kim 
Citation
 BMC Cancer, Vol.18(1) : 158, 2018 
Journal Title
 BMC Cancer 
Issue Date
2018
Keywords
H3K27me3 ; Polycomb repressive complex ; Sarcoma
Abstract
BACKGROUND: Polycomb repressive complex 2 (PRC2; formed by EZH2, SUZ12, and EED protein subunits) and PRC1 (BMI1 protein) induce gene silencing through histone modification by H3K27me3. In the present study, we characterized the PRC expression pattern and its clinical implication in sarcoma. METHODS: Using immunohistochemistry, we analyzed PRC expression in 105 sarcoma patients with 5 subtypes: synovial sarcoma (n = 18), rhabdomyosarcoma (n = 28), Ewing sarcoma (n = 15), osteosarcoma (n = 30), and others (n = 14). RESULTS: The median age at diagnosis in the patient cohort was 26.8 years (range: 1-78 years) and the male-to-female ratio was 1:4. Initial disease presentation was locoregional disease in 83% of patients and initial metastatic disease in the remaining 17%. PRC expression was not significantly different according to histologic subtype (P = 0.400). Overall survival (OS) was significantly poor for SUZ12 high (P = 0.001), EED1 high (P = 0.279), and H3K27me3 high (P = 0.009). Ultimately, patients with PRC2high had significantly inferior OS than the no expression group (P = 0.009). In the Cox proportional hazard model adjusted for stage, histologic grade, surgery, margin and initial metastasis, SUZ12 expression (P = 0.020, HR 29.069, 95% CI 1.690-500.007), H3K27me3 (P = 0.010, HR 3.743, 95% CI 1.370-10.228) expression was significantly associated with shorter OS. CONCLUSION: We detected PRC expression in various sarcomas and demonstrated its independent negative prognostic role, suggesting the PRC axis as promising therapeutic target for treating sarcoma.
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DOI
10.1186/s12885-018-4066-6
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Urology (비뇨의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
Yonsei Authors
김경식(Kim, Kyung Sik) ORCID logo https://orcid.org/0000-0001-9498-284X
김성훈(Kim, Sung Hoon) ORCID logo https://orcid.org/0000-0002-1645-7473
김은경(Kim, Eun Kyung)
김효송(Kim, Hyo Song) ORCID logo https://orcid.org/0000-0002-0625-9828
노성훈(Noh, Sung Hoon) ORCID logo https://orcid.org/0000-0003-4386-6886
라선영(Rha, Sun Young) ORCID logo https://orcid.org/0000-0002-2512-4531
서진석(Suh, Jin Suck) ORCID logo https://orcid.org/0000-0001-9455-9240
안중배(Ahn, Joong Bae) ORCID logo https://orcid.org/0000-0001-6787-1503
이영한(Lee, Young Han) ORCID logo https://orcid.org/0000-0002-5602-391X
정현철(Chung, Hyun Cheol) ORCID logo https://orcid.org/0000-0002-0920-9471
최영득(Choi, Young Deuk) ORCID logo https://orcid.org/0000-0002-8545-5797
한정우(Han, Jung Woo) ORCID logo https://orcid.org/0000-0001-8936-1205
허혁(Hur, Hyuk) ORCID logo https://orcid.org/0000-0002-9864-7229
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162012
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