Article: H3K27me3 protein is a promising predictive biomarker of patients' survival and chemoradioresistance in human nasopharyngeal carcinoma
| Title | H3K27me3 protein is a promising predictive biomarker of patients' survival and chemoradioresistance in human nasopharyngeal carcinoma | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Cai, MY2 Tong, ZT1 2 Zhu, W2 Wen, ZZ2 Rao, HL2 Kong, LL1 Guan, XY2 Kung, HF2 3 Zeng, YX2 Xie, D2 | ||||||
| Issue Date | 2011 | ||||||
| Publisher | The Feinstein Institute for Medical Research. The Journal's web site is located at http://www.molmed.org | ||||||
| Citation | Molecular Medicine, 2011, v. 17 n. 11, p. 1137-1145 [How to Cite?] DOI: http://dx.doi.org/10.2119/molmed.2011.00054 | ||||||
| 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. © 2011 The Feinstein Institute for Medical Research. | ||||||
| ISSN | 1076-1551 2011 Impact Factor: 3.757 2011 SCImago Journal Rankings: 0.442 | ||||||
| DOI | http://dx.doi.org/10.2119/molmed.2011.00054 | ||||||
| ISI Accession Number ID | WOS:000297958800004
Funding Information: 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). | ||||||
| References | References in Scopus |
| dc.contributor.author | Cai, MY | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Tong, ZT | ||||||
| dc.contributor.author | Zhu, W | ||||||
| dc.contributor.author | Wen, ZZ | ||||||
| dc.contributor.author | Rao, HL | ||||||
| dc.contributor.author | Kong, LL | ||||||
| dc.contributor.author | Guan, XY | ||||||
| dc.contributor.author | Kung, HF | ||||||
| dc.contributor.author | Zeng, YX | ||||||
| dc.contributor.author | Xie, D | ||||||
| dc.date.accessioned | 2012-06-26T06:12:08Z | ||||||
| dc.date.available | 2012-06-26T06:12:08Z | ||||||
| dc.date.issued | 2011 | ||||||
| dc.description.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. © 2011 The Feinstein Institute for Medical Research. | ||||||
| dc.description.nature | link_to_OA_fulltext | ||||||
| dc.identifier.citation | Molecular Medicine, 2011, v. 17 n. 11, p. 1137-1145 [How to Cite?] DOI: http://dx.doi.org/10.2119/molmed.2011.00054 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.2119/molmed.2011.00054 | ||||||
| dc.identifier.epage | 1145 | ||||||
| dc.identifier.hkuros | 203483 | ||||||
| dc.identifier.isi | WOS:000297958800004
Funding Information: 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). | ||||||
| dc.identifier.issn | 1076-1551 2011 Impact Factor: 3.757 2011 SCImago Journal Rankings: 0.442 | ||||||
| dc.identifier.issue | 11 | ||||||
| dc.identifier.pmid | 21738951 | ||||||
| dc.identifier.scopus | eid_2-s2.0-82855172243 | ||||||
| dc.identifier.spage | 1137 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/150844 | ||||||
| dc.identifier.volume | 17 | ||||||
| dc.language | eng | ||||||
| dc.publisher | The Feinstein Institute for Medical Research. The Journal's web site is located at http://www.molmed.org | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | Molecular Medicine | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.title | H3K27me3 protein is a promising predictive biomarker of patients' survival and chemoradioresistance in human nasopharyngeal carcinoma | ||||||
| dc.type | Article |
Author Affiliations
- Anhui Medical University
- Sun Yat-Sen University
- Chinese University of Hong Kong