Upper GI
Hideo Takahashi, MD
Surgical Oncology
Mount Sinai South Nassau
Valley Stream, New York, United States
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Introduction: Excessive intercellular connection or confluency is usually limiting factor in the cell culture and apical junction complex is a key component of intercellular cell-to-cell connection. We aimed to investigate gastric cancer biology using Apical Junction Pathway score.
Methods:
Methods: Gene set variant analysis (GSVA) is utilized to obtain Apical Junction Pathway score from gene expression data of the “HALLMARK_APICAL_JUNCTION” gene set. Utilizing the cancer genome atlas (TCGA) and two other large gastric cancer cohorts, we included 1,239 patients in this study.
Results:
Results: The cohorts were dichotomized using the median Apical Junction Pathway score. Apical Junction Pathway enhanced gastric cancer was not consistently associated with cell proliferation or immune cells infiltration. On the other hand, Apical Junction Pathway activated gastric cancer was associated with significantly higher number of stromal cells, including fibroblasts, adipocytes and vascular endothelial cells. These findings suggested that Apical Junction Pathway is activated in gastric cancer with enhanced neovascularization and angiogenesis in the tumor microenvironement (TME). Next, we used gene set enrichment analysis (GSEA) to investigate biology of the high Apical Junction Pathway score group. The high Apical Junction Pathway score group demonstrated increased expression of epithelial mesenchymal transition (EMT) as well as angiogenesis (false discovery rate (FDR) < 0.25). Lastly, gastric cancer with activated Apical Junction Pathway was associated with more aggressive clinicopathological characteristics, such as significantly higher American Joint Committee on Cancer (AJCC) T-category and higher pathological stage. Subsequently, gastric cancer with high Apical Junction Pathway score demonstrated worse Disease-Specific Survival (DSS) and Overall Survival (OS) in all three cohorts (p< 0.05, respectively).
Conclusions:
Conclusion: Gastric cancer with activated Apical Junction Pathway was associated with aggressive clinical characteristics leading to shorter survival likely due to increased metastatic potential from EMT and angiogenesis.