Abstract
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.
Highlights
Esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EA) are the two major histologic types of malignant esophageal neoplasms [1]
Statistical analysis showed that both ESCC and EA tissues had significantly elevated Centrosome-associated protein E (CENPE) expression compared with matched adjacent normal tissues (p = 0.032 and p
CENPE expression was higher in ESCC tissues than in EA tissues (Fig 1F)
Summary
Esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EA) are the two major histologic types of malignant esophageal neoplasms [1]. The overall 5-year survival rate is lower than 20% in both ESCC and EA in the United States [1]. These two subtypes have distinct origins and molecular mechanisms [2, 3]. One recent study showed that ESCC showed stronger molecular similarities to SCCs in other organs, while EA presented a strong molecular resemblance to chromosomally unstable gastric adenocarcinoma [3]. The ESCC and EA have similar 5-year survival rate, it is necessary to explore the specific prognostic indicators in different subtypes of esophageal cancer
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