CALD1 facilitates epithelial-mesenchymal transition progression in gastric cancer cells by modulating the PI3K-Akt pathway

BACKGROUND CALD1 has been discovered to be abnormally expressed in a variety of malignant tumors,including gastric cancer(GC),and is associated with tumor progression and immune infiltration;however,the roles and mechanisms of CALD1 in epithe-lial-mesenchymal transition(EMT)in GC are unknown.AIM To investigate the role and mechanism of CALD1 in GC progression,invasion,and migration.METHODS In this study,the relationship between CALD1 and GC,as well as the possible network regulatory mechanisms of CALD1,was investigated by bioinformatics and validated by experiments.CALD1-siRNA was synthesized and used to trans-fect GC cells.Cell activity was measured using the CCK-8 method,cell migration and invasive ability were measured using wound healing assay and Transwell assay,and the expression levels of relevant genes and proteins in each group of cells were measured using qRT-PCR and Western blot.A GC cell xenograft model RESULTS Bioinformatics results showed that CALD1 was highly expressed in GC tissues,and CALD1 was significantly higher in EMT-type GC tissues than in tissues of other types of GC.The prognosis of patients with high expression of CALD1 was worse than that of patients with low expression,and a prognostic model was constructed and evaluated.The experimental results were consistent with the results of the bioinformatics analysis.The expression level of CALD1 in GC cell lines was all higher than that in gastric epithelial cell line GES-1,with the strongest expression found in AGS and MKN45 cells.Cell activity was significantly reduced after CALD1-siRNA trans-fection of AGS and MKN45 cells.The ability of AGS and MKN45 cells to migrate and invade was reduced after CALD1-siRNA transfection,and the related mRNA and protein expression was altered.According to bioinfor-matics findings in GC samples,the CALD1 gene was significantly associated with the expression of members of the PI3K-AKT-mTOR signaling pathway as well as the EMT signaling pathway,and was closely related to the PI3K-Akt signaling pathway.Experimental validation revealed that upregulation of CALD1 increased the expression of PI3K,p-AKT,and p-mTOR,members of the PI3K-Akt pathway,while decreasing the expression of PTEN;PI3K-Akt inhibitor treatment decreased the expression of PI3K,p-AKT,and p-mTOR in cells overexpressing CALD1(still higher than that in the normal group),but increased the expression of PTEN(still lower than that in the normal group).CCK-8 results revealed that the effect of CALD1 on tumor cell activity was decreased by the addition of the inhibitor.Scratch and Transwell experiments showed that the effect of CALD1 on tumor cell migration and invasion was weakened by the addition of the PI3K-Akt inhibitor.The mRNA and protein levels of EMT-related genes in AGS and MKN45 cells were greatly altered by the overexpression of CALD1,whereas the effect of overex-pression of CALD1 was significantly weakened by the addition of the PI3K-Akt inhibitor.Animal experiments showed that tumour growth was slow after inhibition of CALD1,and the expression of some PI3K-Akt and EMT pathway proteins was altered.CONCLUSION Increased expression of CALD1 is a key factor in the progression,invasion,and metastasis of GC,which may be associated with regulating the PI3K-Akt pathway to promote EMT.

New treatment for gastric duplication cyst:Endoscopic ultrasonography-guided fine-needle aspiration combined with lauromacrogol sclerotherapy:A case report

BACKGROUND Gastric duplication cysts are very rare disease that are mainly diagnosed by endoscopic ultrasonographic fine-needle aspiration biopsy.In the past,this disease was usually treated with traditional surgery and rarely with minimally invasive endoscopic surgery.However,minimally invasive endoscopic therapy has many advantages,such as no skin wound,organ preservation,postoperative pain reduction,early food intake,fewer postoperative complications,and shorter post-procedure hospitalization.CASE SUMMARY We report a case of endoscopic ultrasonography-guided fine-needle aspiration(EUS-FNA)combined with lauromacrogol sclerotherapy for pyloric obstruction due to gastric duplication cysts.CONCLUSION EUS-FNA combined with lauromacrogol sclerotherapy provides a new option for the treatment of gastrointestinal duplication cysts.

Endoscopic diagnosis of early-stage primary esophageal small cell carcinoma: Report of two cases

BACKGROUND Primary esophageal small cell carcinoma(PESCC)is a highly aggressive malignancy,and its detailed clinical behaviors have remained virtually unknown.Because of the rapid tumor progression,the diagnosis of esophageal small cell carcinoma at early stage is extremely difficult in clinical practice.Currently,only a handful of PESCC cases have been reported.CASE SUMMARY Case 1:A 62-year-old man was diagnosed with an esophageal submucosal tumor by endoscopy.Endoscopic ultrasonography showed a 0.8 cm low echo nodule in the muscularis mucosa.As the patient refused to undergo endoscopic resection,neoplasia was detected by endoscopy 1 year later.Case 2:A 68-year-old woman was diagnosed as having an esophageal submucosal tumor by endoscopy at a local hospital.About 2 wk later,we performed endoscopic ultrasonography and found a 1 cm low echo nodule in the muscularis mucosa;the submucosal was thinner than normal but still continuous;mucosal hyperemia and erosion were found on the surface of the tumor.Endoscopic submucosal dissection(ESD)was performed and the histopathological finding showed a small cell carcinoma invading the submucosal layer.CONCLUSION Early esophageal small cell carcinoma shows submucosal infiltrating growth with a hypoechoic mass in the muscularis mucosa as diagnosed by endoscopic ultrasonography.It is easily misdiagnosed as submucosal masses.Endoscopic manifestations should be identified and pathological biopsies should beemployed. ESD may be performed to provide an opportunity for early treatmentof PESCC.