Transcriptome analysis of wild-type (WT) and CDH1 knockout (KO) human Gastric Organoids (hGOs)

We conducted transcriptome analysis usin next generation sequencing of paired WT or CDH1 KO hGO cells established from three patients' fundic gands. Compared to WT hGOs, CDH1 KO hGO cells showed higher expression of matrix metalloproteinase (MMP) genes and genes that regulate inflammation and angiogenesis. We showed that the migration ability of CDH1 KO hGO cells was mediated by upregulation of MMPs and this effect was abolished by specific inhibitor of MMPs in vitro. MMP-3 protein was expressed in clinical samples of E-cadherin deficient signet ring cell carcinoma (SRCC) of the stomach. Our study represents that MMPs are promising candidates for novel therapeutic targets for E-cadherin-deficient SRCC. mRNA profiles of three paired WT and CDH1 KO hGO cells derived from three patients' stomach.