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Molecular Medicine

, Volume 17, Issue 11–12, pp 1137–1145 | Cite as

H3K27me3 Protein Is a Promising Predictive Biomarker of Patients’ Survival and Chemoradioresistance in Human Nasopharyngeal Carcinoma

  • Mu-Yan Cai
  • Zhu-Ting Tong
  • Wei Zhu
  • Zhu-Zhi Wen
  • Hui-Lan Rao
  • Ling-Ling Kong
  • Xin-Yuan Guan
  • Hsiang-Fu Kung
  • Yi-Xin Zeng
  • Dan Xie
Research Article

Abstract

Trimethylation of lysine 27 on histone H3 (H3K27me3) is an epigenetic change which plays a critical role in tumor development and/or progression. However, the molecular status of H3K27me3 and its clinicopathologic/prognostic significance in nasopharyngeal carcinoma (NPC) have not been elucidated. In this study, the methods of Western blotting and immunohistochemistry (IHC) were utilized to examine the expression of H3K27me3 protein in NPC tissues and nonneoplastic nasopharyngeal epithelial tissues. Receiver operating characteristic (ROC) curve analysis was used to determine the cutpoint for H3K27me3 high expression. High expression of H3K27me3 could be observed in 127/209 (60.8%) of NPCs and in 8/50 (16.0%) normal nasopharyngeal epithelial tissues (P < 0.001). Further correlation analysis demonstrated that high expression of H3K27me3 was positively associated with tumor later T classification, tumor metastasis, advanced clinical stage and chemoradioresistance (P < 0.05). Moreover, high expression of H3K27me3 was closely associated with NPC patient shortened survival time as evidenced by univariate and multivariate analysis (P < 0.05). Consequently, a new clinicopathologic prognostic model with three poor prognostic factors (H3K27me3 expression, distant metastasis and treatment regimen) was constructed. The model could stratify risk significantly (low, intermediate and high) for overall survival and progression-free survival (P < 0.0001). These findings provide evidence that H3K27me3 expression, as examined by IHC, has the potential to be used as an immunomarker to predict NPC chemoradiotherapy response and patient prognosis. The combined clinicopathologic prognostic model may become a useful tool for identifying NPC patients with different clinical outcomes.

Notes

Acknowledgments

This work was supported by the 973 Project of China (2010CB912802 and 2010CB529401) and the Foundation of Guangzhou Science and Technology Bureau, China (2005Z1-E0131).

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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Mu-Yan Cai
    • 1
    • 2
  • Zhu-Ting Tong
    • 1
    • 4
  • Wei Zhu
    • 1
  • Zhu-Zhi Wen
    • 3
  • Hui-Lan Rao
    • 1
    • 2
  • Ling-Ling Kong
    • 4
  • Xin-Yuan Guan
    • 1
  • Hsiang-Fu Kung
    • 1
    • 5
  • Yi-Xin Zeng
    • 1
  • Dan Xie
    • 1
  1. 1.State Key Laboratory of Oncology in South China, Cancer CenterSun Yat-Sen UniversityGuangzhouChina
  2. 2.Department of Pathology, Cancer CenterSun Yat-Sen UniversityGuangzhouChina
  3. 3.Department of Cardiology, Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouChina
  4. 4.Department of Radiotherapy, the First Affiliated HospitalAnhui Medical UniversityHefeiChina
  5. 5.The State Key Laboratory of Oncology in South ChinaThe Chinese University of Hong KongShatinHong Kong, China

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