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.
Highlights
Nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-related head and neck cancer, is a leading lethal malignancy with the highest prevalence in Southeast Asia, especially in the Cantonese region of Southern China [1,2]
The trimethylation of H3K27 is mediated by proteins in the Polycomb group (PcG) family of genes which was originally identified as genes suppressing the development of extra sex combs in Drosophila [30]
We found that the majority of NPCs had a higher expression of H3K27me3 than that in adjacent nonneoplastic nasopharyngeal tissues
Summary
Nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-related head and neck cancer, is a leading lethal malignancy with the highest prevalence in Southeast Asia, especially in the Cantonese region of Southern China [1,2]. Early-stage NPC is highly radiocurable, local failure and distant metastasis are still the major issues for the poor outcome of patients with advanced stage NPC [3,4]. Platinum-based induction chemotherapy (IC), followed by chemoradiotherapy (CRT) or radiotherapy (RT), has been utilized to treat locally advanced NPC, which shows benefits for organ preservation, loco-regional control and overall survival [5,6,7]. Despite conventional TNM information having a strong prognostic significance in NPC [8], few predictive biomarkers of response to chemoradiotherapy exist in this cancer. Uncovering predictors of response to IC may improve our ability to anticipate tumor response to CRT or RT and to identify patients who could benefit from a conservative treatment
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