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 PRC2 high 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.
| Original language | English |
|---|---|
| Article number | 158 |
| Journal | BMC cancer |
| Volume | 18 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2018 Feb 7 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Genetics
- Cancer Research
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Prognostic implications of polycomb proteins ezh2, suz12, and eed1 and histone modification by H3K27me3 in sarcoma. / Cho, Yong Jin; Kim, Soo Hee; Kim, Eun Kyung; Han, Jung Woo; Shin, Kyoo Ho; Hu, Hyuk; Kim, Kyung Sik; Choi, Young Deuk; Kim, Sunghoon; Lee, Young Han; Suh, Jin Suck; Ahn, Joong Bae; Chung, Hyun Cheol; Noh, Sung Hoon; Rha, Sun Young; Jung, Sung Taek; Kim, Hyo Song.
In: BMC cancer, Vol. 18, No. 1, 158, 07.02.2018.Research output: Contribution to journal › Article
TY - JOUR
T1 - Prognostic implications of polycomb proteins ezh2, suz12, and eed1 and histone modification by H3K27me3 in sarcoma
AU - Cho, Yong Jin
AU - Kim, Soo Hee
AU - Kim, Eun Kyung
AU - Han, Jung Woo
AU - Shin, Kyoo Ho
AU - Hu, Hyuk
AU - Kim, Kyung Sik
AU - Choi, Young Deuk
AU - Kim, Sunghoon
AU - Lee, Young Han
AU - Suh, Jin Suck
AU - Ahn, Joong Bae
AU - Chung, Hyun Cheol
AU - Noh, Sung Hoon
AU - Rha, Sun Young
AU - Jung, Sung Taek
AU - Kim, Hyo Song
PY - 2018/2/7
Y1 - 2018/2/7
N2 - 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 PRC2 high 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.
AB - 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 PRC2 high 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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UR - http://www.scopus.com/inward/citedby.url?scp=85041809731&partnerID=8YFLogxK
U2 - 10.1186/s12885-018-4066-6
DO - 10.1186/s12885-018-4066-6
M3 - Article
C2 - 29415665
AN - SCOPUS:85041809731
VL - 18
JO - BMC Cancer
JF - BMC Cancer
SN - 1471-2407
IS - 1
M1 - 158
ER -