Molecular Deregulation of in the Pathogenesis of Esophageal Squamous Cell Carcinoma.

Endothelial PAS domain-containing protein 1 (EPAS1) is an angiogenic factor and its implications have been reported in many cancers but not in esophageal squamous cell carcinoma (ESCC). Herein, we aim to examine the genetic and molecular alterations, clinical implications, and functional roles of in ESCC. High-resolution melt-curve analysis and Sanger sequencing were used to detect mutations in sequence. DNA number changes and mRNA expressions were analyzed by polymerase chain reaction. functional assays were used to study the impact of EPAS1 on cellular behaviors. Overall, 7.5% ( = 6/80) of patients with ESCC had mutations in , and eight novel variants (c.1084C>T, c.1099C>A, c.1145_1145delT, c.1093C>G, c.1121T>G, c.1137_1137delG, c.1135_1136insT, and c.1091_1092insT) were detected. Among these mutations, four were frameshift (V382Gfs12, A381Lfs13, K379Ifs6, and K364Nfs12) mutations and showed the potential of non-sense-mediated mRNA decay (NMD) in computational analysis. The majority of patients showed molecular deregulation of [45% ( = 36/80) DNA amplification, 42.5% ( = 34/80) DNA deletion, as well as 53.7% ( = 43/80) high mRNA expression, 20% ( = 16/80) low mRNA expression]. These alterations of were associated with tumor location and T stages. Patients with stage III ESCC having DNA amplification had poorer survival rates in comparison to DNA deletion ( = 0.04). In addition, suppression of in ESCC cells showed reduced proliferation, wound healing, migration, and invasion in comparison to that of control cells. Thus, the molecular and functional studies implied that plays crucial roles in the pathogenesis of ESCC and has the potential to be used as a prognostic marker and as a therapeutic target.