BackgroundPrevious studies have illustrated that checkpoint with forkhead-associated and ring finger domains (CHFR) was frequently silenced in several cancer types due to promoter hypermethylation and functions as a tumor suppressor gene. However, the data from the public dataset reveal that CHFR is highly expressed in human gastric cancer specimens, and the biological function of CHFR in gastric cancer is still not well understood.Materials and methodsThe clinical association between CHFR expression and the overall survival of gastric cancer patients as well as cancer metastasis was analyzed according to public datasets. The CHFR expression in clinical specimens and human gastric cancer cell lines was detected by immunohistochemistry and Western blotting, respectively. Gain (overexpression) and loss (silencing) of function experiments were used to elucidate the role of CHFR in gastric cancer. The migration ability of gastric cancer cells was determined by wound healing and transwell assays. Cell cycle distribution was analyzed using fluorescence-activated cell sorting experiment. The expression of the proteins in cancer cells was measured using Western blot analysis.ResultsAccording to the analysis from Kaplan–Meier plotter dataset, CHFR expression was negatively associated with overall survival of gastric cancer patients. Our data revealed that exogenous expression of CHFR not only arrested cell cycle but also led to dramatically enhanced cell migration, while silencing of CHFR significantly inhibited cell migration in gastric cancer cells. This result is consistent with the data from the Human Cancer Metastasis Dataset, in which CHFR level is found to significantly increase in metastatic gastric cancer. The overexpression of CHFR promoted epithelial–mesenchymal transition (EMT) in both SGC-7901 and AGS cells, while HDAC1 was inhibited. Interestingly, suberoylanilide hydroxamic acid, a HDAC1 antagonist, could effectively increase cell migration in both cell lines via enhancement of EMT.ConclusionOur data indicated that CHFR exerted positive effects on cell migration of human gastric cancer by promoting EMT via downregulating HDAC1.

Rationale:Most of esophageal rupture is a very serious life-threatening benign gastrointestinal tract disease with high mortality. However, there are a few cases of spontaneous esophageal rupture during gastroscopy.Patient concerns:A 57-year-old man who underwent a routine diagnostic gastroscopy due to food obstruction was reported. During the gastroscopy, he vomited severely, which was followed by severe left chest pain radiating into the back and upper abdomen. The diagnosis was made by computed tomography (CT) scan without delay. Enhanced CT showed extensive mediastinal emphysema, a small amount of left pleural effusion, and a 6 cm tear was confirmed in the lower esophagus posteriorly.Diagnoses:The patient was diagnosed with an intrathoracic rupture type of spontaneous esophageal rupture.Interventions:The patient received endoscopic suturing techniques under endotracheal intubation, titanium clip clamping, and over the scope clip (OTSC) sealing.Outcomes:The procedure was smooth and the patient recovered well after operation.Lessons:During gastroscopy, the risk of esophageal rupture should be considered due to sudden pain caused by severe nausea and vomiting. Esophageal rupture can rapidly lead to severe life-threatening infections such as empyema and mediastinitis. Therefore, awareness of this condition is important so that appropriate treatment can rapidly be implemented to increase the likelihood of a good outcome.

Tumor suppressor gene CHFR (The Checkpoint with Forkhead-associated and Ring finger domains) is a mitotic checkpoint and frequently hypermethylated in gastric cancer. Our previous study found CHFR played a certain extent pro-tumor function in gastric cancer. However, little is known about the underlying mechanism. In this study, we tried to further elucidate the role and mechanism for CHFR in gastric cancer (GC) by constructing CHFR stably expressed cell lines. As expected, the ectopic expression of CHFR slowed the cell proliferation in both two SGC-7901 and AGS cells, while significantly promoted the potential of cell migration and invasion. For the first time, our data indicated that stable expression of CHFR in SGC-7901 and AGS restrained cellular reactive oxygen species (ROS) generation and promoted the activation of AKT and ERK, two regulators of redox hemostasis. Furthermore, H2O2 treatment effectively elevated ROS level and reversed CHFR-induced cell invasion in stable SGC-7901 and AGS cells with the decreased phosphorylation of AKT and ERK. We also confirmed that CHFR exerted its function by promoting NRF2 expression. The most important is, the ectopic expression of CHFR significantly inhibited SGC-7901 cell-derived xenografts and obviously promoted lung metastasis of GC cell with NRF2, p-AKT and p-ERK increased. Taken together, our findings suggested that CHFR might take part in gastric cancer progression especially cancer metastasis by activating AKT and ERK via NRF2- ROS axis.