Endothelial PAS domain protein 1 gene hypomethylation is associated with colorectal cancer in Han Chinese

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Abstract
Endothelial PAS domain‑containing protein 1 (EPAS1) serves a role in angiogenesis, which is important for the development of tumors, including colorectal cancer (CRC). The current study aimed to estimate whether EPAS1 methylation was associated with CRC. A two‑stage association study of EPAS1 methylation and CRC was conducted. In the first phase, EPAS1 methylation was evaluated in the tumor and adjacent non‑tumor tissue samples from 41 patients with sporadic CRC in Jiangsu province, China. The diagnostic value of methylation of EPAS1 for CRC in the second phase was evaluated in 79 patients with sporadic CRC and 22 normal individuals in Zhejiang province, China. The methylation assay was performed using a quantitative methylation‑specific polymerase chain reaction (qMSP) method. The percentage of methylated reference (PMR) was used to quantify the methylation level. The first‑stage results indicated that EPAS1 promoter methylation was significantly lower in CRC tumor tissues compared with 5‑cm‑para‑tumor tissues (median PMR, 0.59 vs. 1.22%; P=0.027) and 10‑cm‑para‑tumor tissues (median PMR, 0.59 vs. 1.89%; P=0.001). In addition, the second‑stage results indicated that EPAS1 promoter methylation was significantly lower in tumor tissues compared with 5‑cm‑para‑tumor tissues (median PMR, 1.91 vs. 6.25%; P=3x10‑7) and normal intestinal tissues from healthy controls (median PMR, 1.91 vs. 28.4%; P=5x10‑7). Receiver Operating Characteristic curve analysis of the second‑stage data indicated that the highest area under the curve of EPAS1 hypomethylation was 0.851 between Zhejiang CRC tissues and Zhejiang normal intestinal tissues (sensitivity, 95.5%; specificity, 60.8%).

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