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

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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 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.

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

All Science Journal Classification (ASJC) codes

  • Genetics
  • Oncology
  • Cancer Research

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    Cho, Y. J., Kim, S. H., Kim, E. K., Han, J. W., Shin, K. H., Hu, H., Kim, K. S., Choi, Y. D., Kim, S., Lee, Y. H., Suh, J. S., Ahn, J. B., Chung, H. C., Noh, S. H., Rha, S. Y., Jung, S. T., & Kim, H. S. (2018). Prognostic implications of polycomb proteins ezh2, suz12, and eed1 and histone modification by H3K27me3 in sarcoma. BMC cancer, 18(1), [158]. https://doi.org/10.1186/s12885-018-4066-6