title: H3K27me3 protein is a promising predictive biomarker of patients' survival and chemoradioresistance in human nasopharyngeal carcinoma.
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.
authors: State Key Laboratory of Oncology in South China Department of Pathology, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
authors: Mu-Yan
authors: MY
authors: Cai
authors: Zhu-Ting
authors: ZT
authors: Tong
authors: Wei
authors: W
authors: Zhu
authors: Zhu-Zhi
authors: ZZ
authors: Wen
authors: Hui-Lan
authors: HL
authors: Rao
authors: Ling-Ling
authors: LL
authors: Kong
authors: Xin-Yuan
authors: XY
authors: Guan
authors: Hsiang-Fu
authors: HF
authors: Kung
authors: Yi-Xin
authors: YX
authors: Zeng
authors: Dan
authors: D
authors: Xie
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002277:Carcinoma; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008239:Lysine / Q000378:metabolism*; D008297:Male; D008745:Methylation; D008875:Middle Aged; D008954:Models, Biological; D015999:Multivariate Analysis; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D011379:Prognosis; D012372:ROC Curve; D011836:Radiation Tolerance; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones; D008239:Lysine