Downregulated cytoplasmic polyadenylation element-binding protein-4 is associated with the carcinogenesis of head and neck squamous cell carcinoma.

Manli Zeng,Lin Zhou,Chen Chen,Xingyu Wu,Zezhang Tao,Xiaolin Huang,Lei Wang,Fen Li,Wensheng She

doi:10.3892/ol.2017.7661

Abstract

Cytoplasmic polyadenylation element-binding protein-4 (CPEB4) is involved in several biological processes that are associated with cancer progression. However, it remains unknown whether CPEB4 expression levels are associated with head and neck squamous cell carcinoma (HNSCC). The aim of the present study was to explore the potential function of CPEB4 in HNSCC. The expression of CPEB4 was analyzed in HNSCC from six Gene Expression Omnibus (GEO) datasets. Immunohistochemical staining was conducted to examine CPEB4 protein levels in an HNSCC tissue microarray (TMA). According to the GEO dataset analyses, CPEB4 gene expression was downregulated in HNSCC compared with normal samples (P<0.05). Notably, a statistical difference was observed between different tumor grades (P<0.05). Furthermore, the methylation of the CPEB4 gene in HNSCC was significantly increased compared with that observed in normal samples (P<0.01). The outcome from the TMA demonstrated that CPEB4 protein expression in human HNSCC tumors was significantly decreased compared with normal samples (P<0.05). In addition, the expression of CPEB4 protein was negatively associated with histological grades of HNSCC (P<0.05). The results from the present study suggested that CPEB4 may function as a tumor suppressor gene in HNSCC, which identifies the potential value of CPEB4 in predicting prognosis of HNSCC. Hypermethylation of the CPEB4 gene may be responsible for the downregulation of CPEB4 expression in HNSCC and result in tumorigenesis.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer worldwide, representing 90% of all head and neck cancers [1,2,3]
Results indicated that the Cytoplasmic polyadenylation element‐binding protein‐4 (CPEB4) gene expression level was lower in early‐ and advanced‐stage laryngeal squamous cell carcinoma (LSCC) tumor tissues compared with the tumor margin (P
Ortiz‐Zapater et al [21] initially demonstrated the direct link between CPEB4 expression and cancer etiology, and suggested that overexpression may be a common mechanism for regulating the reprogramming of gene expression involved in cancer progression

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer worldwide, representing 90% of all head and neck cancers [1,2,3]. From 1975‐2010, the morbidity and mortality of patients with HNSCC remained at a high level, with >650,000 novel HNSCC cases diagnosed annually worldwide [6]. A series of biomarkers associated with HNSCC including p16, p53, epidermal growth factor receptor and vascular endothelial growth factor have been identified [7], which have proven to be beneficial in directing diagnosis, prognosis and therapy for this disease. These are insufficient to accurately define the pathogenesis of HNSCC. There is an urgent requirement to explore and identify novel molecular biomarkers that are associated with HNSCC, as potential therapeutic targets

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