Expression of hepatocyte nuclear factor 4 alpha, wingless-related integration site, and beta-catenin in clinical gastric cancer

BACKGROUND Gastric cancer (GC) is the second most common cause of cancer-related deaths worldwide. Hepatocyte nuclear factor 4 alpha (HNF4 alpha) that belongs to the nuclear hormone receptor superfamily, is overexpressed in GC tissues, and might be involved in the development of GC by regulating its downstream wingless-related integration site (WNT)/beta-catenin signaling. AIM To clarify the expression of HNF4 alpha/WNT5a/beta-catenin signaling proteins in clinical GC tissues. METHODS We immunohistochemically stained pathological blocks of GC and matched para-cancerous tissues. The intensity of HNF4 alpha, WNT5a and beta-catenin staining in the tumor cells was determined according to cell rates and staining intensity. The correlations between GC and HNF4 alpha, WNT5a, and beta-catenin expression using chi-square and paired chi-square tests. Relationships between double-positive HNF4 alpha and WNT5a expression and types of gastric tumor tissues were assessed using regression analysis. Correlations between HNF4 alpha and WNT5a expression at the RNA level in GC tissues found in the TCGA database were analyzed using Pearson correlation coefficients. RESULTS We found more abundant HNF4 alpha and WNT5a proteins in GC, especially in mucinous adenocarcinoma and mixed GC than in adjacent tissues (P < 0.001). Low and high levels of cytoplasmic beta-catenin respectively expressed in GC and adjacent tissues (P < 0.001) were not significantly associated with pathological parameters. CONCLUSION The expressions of HNF4 alpha and WNT5a could serve as early diagnostic biomarkers for GC.