Gastric cancer with enhanced apical junction pathway has increased metastatic potential and worse clinical outcomes

Excessive intercellular connection at confluency may be limiting further cell growth or a sign of aggressive biology in the cell culture. As apical junction complex is a main component of cell-to-cell connection, we aimed to investigate gastric cancer biology using Apical Junction Pathway score that we generated using Gene set variant analysis (GSVA) of the "Hallmark Apical Junction" gene set. 1,239 gastric cancer patients from the Cancer Genome Atlas (TCGA) and two GSE cohorts were included in this study. The cohorts were dichotomized using the median of the score. Apical Junction Pathway score high gastric cancer was not consistently associated with increased cell proliferation or immune cell infiltration. On the other hand, Apical Junction Pathway score high gastric cancer was associated with significantly higher infiltration of stromal cells, such as endothelial cells; hence, increased neovascularization and angiogenesis in the tumor microenvironment (TME) were speculated. Gene set enrichment analysis (GSEA) confirmed increased expression of epithelial mesenchymal transition (EMT) and angiogenesis in the high Apical Junction Pathway score group (false discovery rate (FDR) <0.25). Lastly, the high Apical Junction Pathway score group was associated with more aggressive clinicopathological characteristics, such as significantly higher American Joint Committee on Cancer (AJCC) T-category and higher pathological stage, leading to worse disease-specific survival and overall survival (P<0.05, respectively). In conclusion, enhanced Apical Junction Pathway score gastric cancer was associated with aggressive clinical characteristics leading to shorter survival likely due to increased metastatic potential from EMT and angiogenesis.