Tianyi Dong

The pathogenesis of gastric cancer is not completely understood. Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) has recently been identified as a novel negative regulator gene of the immune system, and studies in mice and humans have suggested its inhibitory action in both inflammation and cancer. In this study, we examined the expression levels of TIPE2 in human gastric cancer tissues and also samples of paraneoplastic control tissue, and found that TIPE2 expression was reduced in gastric cancer. To investigate the role of TIPE2 in gastric cell carcinogenesis, a TIPE2 plasmid was introduced into gastric cell lines and TIPE2 function was examined. Colony-forming assays showed that restoration of TIPE2 expression in gastric cells significantly suppressed cell proliferation. Analysis by flow cytometry showed that the number of cells in the S phase of the cell cycle was reduced concomitant with TIPE2 expression, and cell apoptosis was maintained at a low level. Microarray and western blot analyses revealed that TIPE2 selectively up-regulated N-ras and p27 expression. The role of p27 in mediating TIPE2-associated cell growth inhibition was verified by a p27 siRNA interference assay. In this study, we proved that TIPE2 is an inhibitor of gastric cancer cell growth, and suggest that TIPE2 might promote a p27-associated signaling cascade that leads to restored control of the cell cycle and cell division. Our results provide a new molecular mechanism by which TIPE2 may regulate proliferation of gastric cells.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has caused a global pandemic, resulting in considerable mortality. The risk factors, clinical treatments, especially comprehensive risk models for COVID-19 death are urgently warranted. METHODS: In this retrospective study, 281 non-survivors and 712 survivors with propensity score matching by age, sex, and comorbidities were enrolled from January 13, 2020 to March 31, 2020. RESULTS: Higher SOFA, qSOFA, APACHE II and SIRS scores, hypoxia, elevated inflammatory cytokines, multi-organ dysfunction, decreased immune cell subsets, and complications were significantly associated with the higher COVID-19 death risk. In addition to traditional predictors for death risk, including APACHE II (AUC = 0.83), SIRS (AUC = 0.75), SOFA (AUC = 0.70) and qSOFA scores (AUC = 0.61), another four prediction models that included immune cells subsets (AUC = 0.90), multiple organ damage biomarkers (AUC = 0.89), complications (AUC = 0.88) and inflammatory-related indexes (AUC = 0.75) were established. Additionally, the predictive accuracy of combining these risk factors (AUC = 0.950) was also significantly higher than that of each risk group alone, which was significant for early clinical management for COVID-19. CONCLUSIONS: The potential risk factors could help to predict the clinical prognosis of COVID-19 patients at an early stage. The combined model might be more suitable for the death risk evaluation of COVID-19.