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

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

Research output: Contribution to journalArticle

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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 languageEnglish
Article number158
JournalBMC cancer
Volume18
Issue number1
DOIs
Publication statusPublished - 2018 Feb 7

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Histone Code
Sarcoma
Survival
Polycomb Repressive Complex 2
Proteins
Synovial Sarcoma
Ewing's Sarcoma
Rhabdomyosarcoma
Protein Subunits
Gene Silencing
Osteosarcoma
Proportional Hazards Models
Immunohistochemistry
Neoplasm Metastasis

All Science Journal Classification (ASJC) codes

  • Oncology
  • Genetics
  • Cancer Research

Cite this

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. / Prognostic implications of polycomb proteins ezh2, suz12, and eed1 and histone modification by H3K27me3 in sarcoma. In: BMC cancer. 2018 ; Vol. 18, No. 1.
@article{534159ebf2d94628acc5589b85a47d86,
title = "Prognostic implications of polycomb proteins ezh2, suz12, and eed1 and histone modification by H3K27me3 in 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 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.",
author = "Cho, {Yong Jin} and Kim, {Soo Hee} and Kim, {Eun Kyung} and Han, {Jung Woo} and Shin, {Kyoo Ho} and Hyuk Hu and Kim, {Kyung Sik} and Choi, {Young Deuk} and Sunghoon Kim and Lee, {Young Han} and Suh, {Jin Suck} and Ahn, {Joong Bae} and Chung, {Hyun Cheol} and Noh, {Sung Hoon} and Rha, {Sun Young} and Jung, {Sung Taek} and Kim, {Hyo Song}",
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doi = "10.1186/s12885-018-4066-6",
language = "English",
volume = "18",
journal = "BMC Cancer",
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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 journalArticle

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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U2 - 10.1186/s12885-018-4066-6

DO - 10.1186/s12885-018-4066-6

M3 - Article

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AN - SCOPUS:85041809731

VL - 18

JO - BMC Cancer

JF - BMC Cancer

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