UGT2B17 and miR-224 contribute to hormone dependency trends in adenocarcinoma and squamous cell carcinoma of esophagus

Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA) are the two main subtypes of esophageal cancer. Genetics underpinnings of EA are substantially less understood than that of ESCC. A large-scale relation data analysis was conducted to explore the genes implicated with either EA or ESCC, or both. Each gene linked to ESCC but not EA was further explored in mega-analysis of six independently collected EA RNA expression datasets. A multiple linear regression (MLR) model was built to study the possible influence of sample size, population region, and study date on the gene expression data in EA. Finally, a functional pathway analysis was conducted to identify the possible linkage between EA and the genes identified as novel significant contributors. We have identified 276 genes associated with EA, 1088 with ESCC, with a significant (P<5.14e-143) overlap between these two gene groups (n=157). Mega-analysis showed that two ESCC-related genes, UGT2B17 and MIR224, were significantly associated with EA (P-value <1e-10), with multiple connecting pathways revealed by functional analysis. ESCC and EA share some common pathophysiological pathways. Further study of UGT2B17 and MIR224, which are differentially dysregulated in ESCC and EA tumors, is warranted. Enhanced expression of UGT2B17 and the lack of miR-224 signaling may contribute to the responsiveness of EA to the male sex steroids.