CENPE expression is associated with its DNA methylation status in esophageal adenocarcinoma and independently predicts unfavorable overall survival

Centrosome-associated protein E (CENPE) is a plus end-directed kinetochore motor protein, which plays a critical role in mitosis. In this in silico study, using data from the Cancer Genome Atlas-Esophageal Carcinoma (TCGA-ESCA), we analyzed the expression profile of CENPE mRNA in esophageal squamous...

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Published in:	PloS one 2019-02, Vol.14 (2), p.e0207341-e0207341
Main Authors:	Zhu, Xueqiang, Luo, Xing, Feng, Gang, Huang, Hui, He, Yangke, Ma, Wen, Zhang, Changqing, Zeng, Ming, Liu, Hao
Format:	Article
Language:	eng
Subjects:	Adenocarcinoma Adenocarcinoma - genetics Adenocarcinoma - pathology Aged Biology and life sciences Biomarkers, Tumor - genetics Cancer genetics Cancer research Carcinoma Care and treatment Chromosomal Proteins, Non-Histone - genetics Chromosomes Continuity (mathematics) CpG islands CpG Islands - genetics Deoxyribonucleic acid DNA DNA methylation DNA Methylation - genetics Epigenetics Esophageal cancer Esophageal carcinoma Esophageal Neoplasms - genetics Esophageal Neoplasms - pathology Esophageal Squamous Cell Carcinoma - genetics Esophageal Squamous Cell Carcinoma - pathology Esophagus Female Gene expression Gene Expression Regulation, Neoplastic - genetics Genetic aspects Genetic Association Studies - methods Genomes Genomics Humans Kaplan-Meier Estimate Male Medicine and Health Sciences Messenger RNA Methylation Mitosis Molecular motors (Biochemistry) mRNA Multivariate analysis Operating systems (Software) Ovarian cancer Physical Sciences Prognosis Proteins Radiation therapy Research and Analysis Methods Risk factors RNA Squamous cell carcinoma Survival Tissues Up-Regulation - genetics
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Summary:	Centrosome-associated protein E (CENPE) is a plus end-directed kinetochore motor protein, which plays a critical role in mitosis. In this in silico study, using data from the Cancer Genome Atlas-Esophageal Carcinoma (TCGA-ESCA), we analyzed the expression profile of CENPE mRNA in esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EA), its independent prognostic value and the potential mechanisms of its dysregulation in EA. Results showed that both ESCC and EA tissues had significantly elevated CENPE expression compared with their respective adjacent normal tissues. However, Kaplan-Meier survival curves showed that high CENPE was associated with unfavorable OS in EA. Univariate and multivariate analysis confirmed that CENPE expression was an independent indicator of unfavorable OS in EA patients, as a continuous variable (HR: 1.861, 95%CI: 1.235-2.806, p = 0.003) or as categorical variables (HR: 2.550, 95%CI: 1.294-5.025, p = 0.007). However, CENPE expression had no prognostic value in ESCC. Compared with the methylation status in normal samples, 3 CpG sites were hypomethylated (cg27388036, cg27443373, and cg24651824) in EA, among which two sites (cg27443373 and cg24651824) showed moderately negative correlation with CENPE expression. In addition, we also found that although heterozygous loss (-1) was frequent in EA (50/88, 56.8%), it was not necessarily associated with decreased CENPE expression compared with the copy neutral (0) cases. The methylation of the -1 group was significantly lower than that of the +1/0 group (p = 0.04). Based on these findings, we infer that CENPE upregulation in EA might serve as a valuable indicator of unfavorable OS. The methylation status of cg27443373 and cg24651824 might play a critical role in modulating CENPE expression.
ISSN:	1932-6203 1932-6203