BackgroundGlutathione peroxidase 8 (GPX8) is a type II transmembrane protein with rare structural features belonging to the glutathione peroxidase family. The function of GPX8 in stomach adenocarcinoma has not been discovered clearly.MethodsIn this study, we comprehensively analyzed the expression of GPX8 in stomach adenocarcinoma and discovered that it is a potential target in the treatment of stomach adenocarcinoma. The immunohistochemical staining of GPX8 and survival analysis were performed in carcinoma tissue and adjacent tissues of 83 gastric cancer patients. The Gene Expression Profiling Interactive Analysis (GEPIA) database and Kaplan–Meier plotter database were used to evaluate the prognostic survival of GPX8 in stomach adenocarcinoma. The Cancer Genome Atlas (TCGA) database was used to download the microarray mRNA data of GPX8 and clinical information for cancer patients. The TIMER database and GSEA database were used to systematically evaluate the association of GPX8 and tumor-infiltrating lymphocytes in adenocarcinoma carcinoma. The STRING database was used to analyze protein-to-protein interactions of GPX8. The ROC curve was used to analyze the diagnostic effect of GPX8 in distinguishing outcomes between different subgroups, and a nomogram was constructed based on GPX8. Top transcription factor binding sites were analyzed using the QIAGEN database in the GPX8 gene promoter, and the functional enrichment analysis of GPX8 was done by GO and KEGG pathway enrichment analyses.ResultBased on the GEPIA and TCGA databases, the mRNA expression of GPX8 was significantly higher in stomach adenocarcinoma compared with the adjacent normal tissues. The GEPIA and Kaplan–Meier plotter databases showed that a higher GPX8 expression level was correlated with poor prognosis of stomach adenocarcinoma, suggesting that GPX8 was a risk factor of poor prognosis in stomach adenocarcinoma. The TIMER database showed that the GPX8 expression level was positively correlated with infiltrating levels of CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in stomach adenocarcinoma. The GSEA database indicated that GPX8 was positively correlated with B cells, dendritic cells, CD4+ T cells, CD8+ T cells, macrophages, mast cells, monocytes, and natural killer cells. At last, GO analysis indicated that the biological processes were enriched in collagen fibril organization, endodermal cell differentiation, collagen metabolic process, extracellular matrix organization, etc. KEGG signaling pathway analysis showed that GPX8 was correlated with protein digestion and absorption, extracellular matrix receptor interaction, AGE/RAGE signaling pathway, etc. The GSEA database showed that GPX8 was positively associated with angiogenesis, epithelial mesenchymal transition, hedgehog signaling, etc. The immunohistochemical staining of GPX8 and survival analysis in 83 gastric cancer patients showed that the OS rate of patients with a high GPX8 expression was significantly lower than that of the low GPX8 expression group.ConclusionGPX8 is an important factor which might be a potential target in the treatment of stomach adenocarcinoma.
BackgroundThe prognostic prolongation effect of surgical resection in the management of gastric neuroendocrine carcinoma (GNEC) with distant metastases was still uncertain. The purpose of this study was to investigate the association of primary tumor resection (PTR) with outcomes in patients with stage IV GNEC.MethodsThis retrospective study analyzed patients with distant metastatic GNEC diagnosed between 2000 and 2018 and identified using the Surveillance, Epidemiology, and End Results (SEER) database. Patients were divided into PTR and non-PTR groups. The stabilized inverse probability of treatment weighting (IPTW) method was used to reduce the selection bias. Overall survival (OS) and cancer-specific survival (CSS) were estimated using the Kaplan–Meier method and log-rank test. Cox-regression analyses (uni- and multivariate) were performed to evaluate factors potentially influencing survival.ResultsA total of 126 patients with a median follow-up of 79 months were identified. Forty-four patients underwent PTR and 82 patients did not undergo surgery. After the IPTW approach, PTR improved the OS in patients with stage IV GNEC (median OS 12 vs. 6 months, P = 0.010). The 1- and 3-year OS for patients with or without PTR were 43.8% and 34.5%, and 27.9% and 6.5%, respectively. The median CSS was 12 months for patients undergoing PTR and 6 months for those who did not. The 1 and 3-year CSS for patients with or without PTR were 45.1% and 37.0%, and 27.9% and 6.5%, respectively. In IPTW-adjusted Cox proportional hazards regression analysis, PTR was recognized as an independent factor for improved survival after the occurrence of distant metastatic disease [OS: hazard ratio (HR) = 0.305; 95% confidence interval (CI): 0.196, 0.475; and CSS: HR = 0.278; 95% CI: 0.171, 0.452].ConclusionPTR for stage IV GNEC contributes to a better prognosis compared with non-surgery. This study supported the resection of the primary tumor in patients with distant metastatic GNEC.
It was generally believed that the prognosis of gastric neuroendocrine carcinoma (GNEC) was worse than gastric adenocarcinoma (GAC). However, almost all previous studies compared the prognosis of GNEC and GAC based on East Asians. In this study, we evaluated the clinicopathological features and prognosis of GNEC and GAC in Whites. Patients with GNEC and GAC were identified from 2000 to 2018 in the Surveillance, Epidemiology, and End Results (SEER) database. We used propensity score matching (PSM) analysis to match the age, sex, TNM stage, and treatments received between GNEC and GAC, then compared the overall survival (OS) and cancer-specific survival (CSS) in the two types. A total of 392 cases of GNEC and 12,835 cases of GAC in Whites were recognized. After PSM, the 5-year OS rates of GNEC and GAC were 50.3% and 43.0%, respectively (p = 0.010). The 5-year CSS rates of GNEC and GAC were 57.4% and 50.1%, respectively (p = 0.012). Besides, multivariable cox regression analyses showed that GNEC was an independent predictor of improved OS (HR 0.719; 95% CI 0.607–0.853) and CSS (HR 0.691; 95% CI 0.571–0.835) in the matched data. The prognosis of GNEC was better than GAC in Whites, showing significant ethnic differences. Appropriate treatments and follow-up strategies for GNEC in Whites are probably different from East Asians. The potential genetic and molecular mechanisms need to be further explored.
BACKGROUND The tumor microenvironment (TME) plays an important role in the growth and expansion of gastric cancer (GC). Studies have identified that CD93 is involved in abnormal tumor angiogenesis, which may be related to the regulation of the TME. AIM To determine the role of CD93 in GC. METHODS Transcriptomic data of GC was investigated in a cohort from The Cancer Genome Atlas. Additionally, RNA-seq data sets from Gene Expression Omnibus (GSE118916, GSE52138, GSE79973, GSE19826, and GSE84433) were applied to validate the results. We performed the immune infiltration analyses using ESTIMATE, CIBERSORT, and ssGSEA. Furthermore, weighted gene co-expression network analysis (WGCNA) was conducted to identify the immune-related genes. RESULTS Compared to normal tissues, CD93 significantly enriched in tumor tissues ( t = 4.669, 95%CI: 0.342-0.863, P < 0.001). Higher expression of CD93 was significantly associated with shorter overall survival (hazard ratio = 1.62, 95%CI: 1.09-2.4, P = 0.017), less proportion of CD8 T and activated natural killer cells in the TME ( P < 0.05), and lower tumor mutation burden ( t = 4.131, 95%CI: 0.721-0.256, P < 0.001). Genes co-expressed with CD93 were mainly enriched in angiogenesis. Moreover, 11 genes were identified with a strong relationship between CD93 and the immune microenvironment using WGCNA. CONCLUSION CD93 is a novel prognostic and diagnostic biomarker for GC, that is closely related to the immune infiltration in the TME. Although this retrospective study was a comprehensive analysis, the prospective cohort studies are preferred to further confirm these conclusions.
Obstructive jaundice (OJ) is a common problem in daily clinical practice. However, completely understanding the pathophysiological changes in OJ remains a challenge for planning current and future management. The effects of OJ are widespread, affecting the biliary tree, hepatic cells, liver function, and causing systemic complications. The lack of bile in the intestine, destruction of the intestinal mucosal barrier, and increased absorption of endotoxins can lead to endotoxemia, production of proinflammatory cytokines, and induce systemic inflammatory response syndrome, ultimately leading to multiple organ dysfunction syndrome. Proper management of OJ includes adequate water supply and electrolyte replacement, nutritional support, preventive antibiotics, pain relief, and itching relief. The surgical treatment of OJ depends on the cause, location, and severity of the obstruction. Biliary drainage, surgery, and endoscopic intervention are potential treatment options depending on the patient's condition. In addition to modern medical treatments, Traditional Chinese medicine may offer therapeutic benefits for OJ. A comprehensive search was conducted on PubMed for relevant articles published up to August 1970. This review discusses in detail the pathophysiological changes associated with OJ and presents effective strategies for managing the condition.
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