Cancer Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Division of Thoracic Surgery, Department of Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
PLoS One. 2019 Feb 4;14(2):e0207341. doi: 10.1371/journal.pone.0207341. eCollection 2019.
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.
中心体相关蛋白 E（CENPE）是一种向正极方向运动的动粒马达蛋白，在有丝分裂中发挥关键作用。在这项计算机研究中，我们使用癌症基因组图谱-食管鳞癌（TCGA-ESCA）的数据，分析了 CENPE mRNA 在食管鳞癌（ESCC）和腺癌（EA）中的表达谱，及其在 EA 中失调的独立预后价值和潜在机制。结果表明，与各自的相邻正常组织相比，ESCC 和 EA 组织的 CENPE 表达均显著升高。然而，Kaplan-Meier 生存曲线显示，CENPE 高表达与 EA 患者的不良 OS 相关。单因素和多因素分析证实，CENPE 表达是 EA 患者不良 OS 的独立指标，无论是作为连续变量（HR：1.861，95%CI：1.235-2.806，p = 0.003）还是作为分类变量（HR：2.550，95%CI：1.294-5.025，p = 0.007）。然而，CENPE 表达在 ESCC 中没有预后价值。与正常样本的甲基化状态相比，在 EA 中，有 3 个 CpG 位点（cg27388036、cg27443373 和 cg24651824）呈低甲基化状态，其中 2 个位点（cg27443373 和 cg24651824）与 CENPE 表达呈中度负相关。此外，我们还发现，尽管 EA 中杂合性缺失（-1）较为常见（50/88，56.8%），但与拷贝中性（0）病例相比，其 CENPE 表达不一定降低。-1 组的甲基化水平明显低于+1/0 组（p = 0.04）。基于这些发现，我们推断 EA 中 CENPE 的上调可能是不良 OS 的一个有价值的指标。cg27443373 和 cg24651824 的甲基化状态可能在调节 CENPE 表达中发挥关键作用。
