The Transition from Gastric Intestinal Metaplasia to Gastric Cancer Involves and Downregulation.

Intestinal metaplasia (IM) is an intermediate step in the progression from premalignant to malignant stages of gastric cancer (GC). The Popeye domain containing () gene family encodes three transmembrane proteins, POPDC1, POPDC2, and POPDC3, initially described in muscles and later in epithelial and other cells, where they function in cell-cell interaction, and cell migration. and downregulation was described in several tumors, including colon and gastric cancers. We questioned whether IM-to-GC transition involves gene dysregulation. Gastric endoscopic biopsies of normal, IM, and GC patients were examined for expression levels of and several suggested IM biomarkers, using immunohistochemistry and qPCR. Immunostaining indicated lower POPDC1 and POPDC3 labeling in IM compared with normal tissues. Significantly lower and mRNA levels were measured in IM and GC biopsies and in GC-derived cell lines. The reduction in focal IM was smaller than in extensive IM that resembled GC tissues. and transcript levels were highly correlated with each other and inversely correlated with , , , and several mucin transcripts. The association of and downregulation with IM-to-GC transition implicates a role in tumor suppression and highlights them as potential biomarkers for GC progression and prospective treatment targets.