Abstract: Objective To investigate the expression of Wnt1 induced signaling pathway protein-1 (WISP1) in gastric adenocarcinoma and its relationship with prognosis. Methods Immunohistochemical staining was used to analyze the expression and correlation of WISP1, vascular endothelial growth factor (VEGF), Twist1 and matrix metalloproteinase (MMP) -2 in 200 cases of gastric adenocarcinoma, and the relationship between WISP1 and prognosis of stomach adenocarcinoma. Meanwhile, the expression differences of WISP1 in gastric adenocarcinoma and adjacent tissues, the correlation between WISP1 and clinical prognosis were analyzed in the Cancer Genome Atlas database by the GEPIA (Gene Expression profiling interactive analysis) and UALCAN online tools. R package was used to analyze the expression of WISP1 in GSE13861 gastric adenocarcinoma data set and the correlation between WISP1 and Twist 1 in TCGA database. In addition, based on TCGA database and GSE13861 gastric adenocarcinoma data set, WISP1 gene was selected for Gene Ontology, Kyoto Encyclopedia of Genes and Genomes by R package and Gene Set Enrichment Analysis by Gene Set Enrichment software. Results Immunohistochemical staining showed that 116 cases (58%) were positive and 84 cases (42%) were negative in 200 cases of gastric adenocarcinoma. The positive rates of WISP1 expression were higher in TNM Ⅲ- Ⅳ stage, lymph node metastasis, distant metastasis and/or recurrence patients (P＜0.05), and the survival time of patients with WISP1 positive expression was shorter than that of patients with negative expression (24 months vs. 52 months, Log rank χ2=5.368, P＜0.05). TCGA database and GSE13861 gastric adenocarcinoma data set showed that the expression level of WISP1 was significantly higher in gastric adenocarcinoma tissue than that in adjacent tissue and normal gastric tissue (P＜ 0.05). The survival time of patients with high WISP1 expression was short analyzed by online tools. In addition, immunohistochemical results showed that VEGF, Twist1 and MMP-2 protein were highly expressed in WISP1 positive group (P＜0.05). WISP1 was positively correlated with the expressions of VEGF, CDH5, MMP-2, MMP-9, Snail, Twist1 and Vimentin, but negatively correlated with the expression of CDH1 (P＜0.05). GO analysis showed that WISP1 gene was involved in the biological processes of single cell migration, extracellular matrix structure and intercellular adhesion. WISP1 gene showed the molecular function of binding integrin and collagen, and molecular function of activating cytokines. KEGG pathway enrichment analysis showed that WISP1 was involved in the signal transduction pathway of extracellular matrix binding and cell adhesion. GSEA enrichment results showed that when WISP1 was over-expressed, the genes related to angiogenesis and EMT were up-regulated. Conclusion WISP1 is highly expressed at gene and protein levels in gastric adenocarcinoma, which may be involved in the metastasis and/or recurrence of gastric adenocarcinoma by promoting angiogenesis or EMT.

Key words: stomach neoplasms, adenocarcinoma, Wnt1 protein, neoplasm metastasis, recurrence, epithelialmesenchymal transition, TCGA database, GEO database