Immunotherapy based on immune checkpoint inhibitors (ICIs) is considered to be a promising treatment for stomach adenocarcinoma (STAD), but only a minority of patients benefit from it. It is believed that the poor therapeutic efficacy is attributed to the complex tumor immune microenvironment (TIM) of STAD. Therefore, elucidating the specific regulatory mechanism of TIM in STAD is critical. Previous study suggests that GRP176 may be involved in regulating the pace of circadian behavior, and its role in tumors has not been reported. In this study, we first found that GPR176 was highly expressed in STAD and negatively correlated with patient prognosis. Next, we investigated the relationship between GPR176 and clinical characteristics, and the results showed that the stage is closely related to the level of GPR176. In addition, our further analysis found that GRP176 expression level was significantly correlated with chemotherapeutic drug sensitivity and ICI response. KEGG and GO analyses showed that GPR176 might be involved in stromal remodeling of STAD. Furthermore, we analyzed the association between GPR176 expression and immune implication, and the results revealed that GPR176 was negatively related to the infiltration of various immune cells. Interestingly, GPR176 induced the conversion of TIM while reducing the tumor immune burden (TMB). The expression of GRP176 is closely related to the level of various immunomodulators. Moreover, we performed univariate and multivariate regression analyses on the immunomodulators and finally obtained 4 genes (CRCR4, TNSF18, PDCD1, and TGFB1). Then, we constructed a GRP176-related immunomodulator prognostic model (GRIM) based on the above 4 genes, which was validated to have good predictive power. Finally, we developed a nomogram based on the risk score of GRIM and verified its accuracy. These results suggested that GPR176 is closely related to the prognosis and TIM of STAD. GPR176 may be a new potential target for immunotherapy in STAD.

Background:A comprehensive assessment of the burden of intestinal obstruction was important in determining prevention strategies for the disease. We presented the trends in disease burden and its epidemiological features in China from 1990 to 2019 in order to provide a reference for the prevention of intestinal obstruction. Methods: The GBD 2019 database was searched to obtain relevant data. The data we use included the prevalent cases, prevalence, incident cases, incidence, DALYs, DALY rate, and SDI for global and China. We analyzed the epidemiological age-period-cohort trend of intestinal obstruction in China from 1990 to 2019, and explored the relationship between the incidence and DALY rate and SDI. Result: The incidence of intestinal obstruction in China increased in the last 30 years from 1990 to 2019, but the increase was not significant and remained stable in recent years. Among them, the incidence of 10-14 years youth group was the lowest, the incidence of 1-4 years infants’ group was higher, and the 85-89 years age group had the highest incidence, while the DALY rate decreased significantly with the obviously rise in SDI levels. Conclusion: The disease burden of intestinal obstruction in China decreased to some extent from 1990 to 2019, which was negatively correlated with the level of social development. However, the prevention of intestinal obstruction in the elderly, infants and children still needs to be stepped up.