Gastric cancer is the third leading cause of cancer death worldwide. In this study, we tried to clarify the function of KLF5 in gastric cancer. Copy number variation (CNV) and the expression of KLF5 were interrogated in public datasets. The clinical significance of KLF5 amplification and gene expression in gastric cancer were evaluated. The function of KLF5 in cell proliferation was studied in gastric cancer cell lines and organoids. We found that KLF5 amplification mainly occurred in the chromosome instable tumors (CIN) and was significantly associated with TP53 mutation. In addition, higher KLF5 expression correlated with more locally invasive gastric cancer and higher T stage. Next, a KLF5 gene expression signature was curated. The genes in the signature were involved in cell development, cell cycle regulation, cell death, suggesting potential roles played by KLF5. Functional studies using siRNAs revealed that KLF5 was essential for the proliferation of gastric cancer cells. Finally, using gastric organoid models, we revealed that the proliferation of organoids was significantly inhibited after the down regulation of KLF5. Our study revealed that KLF5 was amplified and over-expressed in gastric cancer, and it may play an oncogene-like role in gastric cancer by supporting cell proliferation.

No abstract

ObjectivesThis study aimed to demonstrate the feasibility and safety of a novel twin‐grasper assisted mucosal inverted closure (TAMIC) technique for large perforations after gastric endoscopic full‐thickness resection (EFTR) in a porcine model.MethodsIatrogenic large perforations of the stomach were created and closed by an experienced endoscopist using the TAMIC technique in 12 pigs. Repeat gastroscopy was performed in 4 weeks after surgery to examine the wound sites and then the animals were killed. The primary outcomes were the successful TAMIC closure rate and the complete healing rate. Secondary end points included procedure time of TAMIC, complete inverted healing rate, delayed bleeding rate, and postsurgery perforation. Histologies of the wounds were analyzed by hematoxylin–eosin, Masson trichrome, and immunohistochemistry staining.ResultsThe median size of the defects was 3.5 (range 2.5–4.5) cm. TAMIC was successfully performed in all the 12 pigs. Complete healing was achieved in 11 pigs 4 weeks after operation as one pig died postsurgery due to severe pneumonia. The median procedure time for TAMIC was 39 (range 23–81) min. The complete inverted healing rate was 45.5% (5/11). No delayed bleeding or postsurgery perforation was observed. Histologic analyses showed that both the epithelium and muscularis mucosae layers were appropriately connected under inverted healing.ConclusionsTwin‐grasper assisted mucosal inverted closure is feasible and safe for closure of large perforations after gastric EFTR and could be a propagable and promising technique for clinical practice.