ABSTRACT
OBJECTIVE@#To explore the driving gene of hepatocellular carcinoma (HCC) occurrence and progression and its potential as new therapeutic target of HCC.@*METHODS@#The transcriptome and genomic data of 858 HCC tissues and 493 adjacent tissues were obtained from TCGA, GEO, and ICGC databases. Gene Set Enrichment Analysis (GSEA) identified EHHADH (encoding enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase) as the hub gene in the significantly enriched differential pathways in HCC. The downregulation of EHHADH expression at the transcriptome level was found to correlate with TP53 mutation based on analysis of the TCGA- HCC dataset, and the mechanism by which TP53 mutation caused EHHADH downregulation was explored through correlation analysis. Analysis of the data from the Metascape database suggested that EHHADH was strongly correlated with the ferroptosis signaling pathway in HCC progression, and to verify this result, immunohistochemical staining was used to examine EHHADH expression in 30 HCC tissues and paired adjacent tissues.@*RESULTS@#All the 3 HCC datasets showed signficnatly lowered EHHADH expression in HCC tissues as compared with the adjacent tissues (P < 0.05) with a close correlation with the degree of hepatocyte de-differentiation (P < 0.01). The somatic landscape of HCC cohort in TCGA dataset showed that HCC patients had the highest genomic TP53 mutation rate. The transcriptomic level of PPARGC1A, the upstream gene of EHHADH, was significantly downregulated in HCC patients with TP53 mutation as compared with those without the mutation (P < 0.05), and was significantly correlated with EHHADH expression level. GO and KEGG enrichment analyses showed that EHHADH expression was significantly correlated with abnormal fatty acid metabolism in HCC. The immunohistochemical results showd that the expression level of EHHADH in HCC tissues was down-regulated, and its expression level was related to the degree of hepatocytes de-differentiation and the process of ferroptosis.@*CONCLUSION@#TP53 mutations may induce abnormal expression of PPARGC1A to cause downregulation of EHHADH expression in HCC. The low expression of EHHADH is closely associated with aggravation of de-differentiation and ferroptosis escape in HCC tissues, suggesting the potential of EHHADH as a therapeutic target for HCC.
Subject(s)
Humans , Carcinoma, Hepatocellular/genetics , Transcriptome , Liver Neoplasms/genetics , Gene Expression Profiling , Fatty Acids , Peroxisomal Bifunctional EnzymeABSTRACT
Context: C-Cbl is an important negative regulator of the cell signaling that acts as an adaptor protein and E3 ubiquitin ligase. The role of c-Cbl in development and regulation of human cancer has aroused intensive attention. Aims: In this study, we aimed to assess the correlation between the expression of c-Cbl and clinicopathological parameters and explored the role of c-Cbl in the development and progression of GC. Settings and Design: This is a Pilot study. Methods and Materials: In total, 84 tissue samples including 44 gastric cancers (GC) and 40 matched adjacent normal tissues were collected after surgery. Then tissue microarray (TMA) and immunohistochemistry (IHC) technology were combined to detect the protein expression of c-Cbl. Statistical Analysis Used: Statistical analysis was performed using SPSS 22.0 (IBM Corporation, Armonk, NY, USA). Results: We have studied the correlation between c-Cbl expression and clinicopathological parameters. Our study showed that c-Cbl has a low expression in 61.4% (27/44) of GC tissues, and the incidence of cases was significantly higher than that in adjacent normal tissues (P < 0.0001). In addition, the correlation between c-Cbl expression and gastric carcinoma subtype (P = 0.027), histological type (P = 0.033), Borrmann classification (P = 0.009), histological differentiation (P = 0.0005), lymph node metastasis (P = 0.007), and intravascular tumor thrombus (P = 0.036) has also been revealed. Conclusions: Our results show that c-Cbl is down-regulated in GC tissues compared with normal gastric tissue, which may play an important role in the development and progression of GC.
ABSTRACT
In the past two years, a line of basic and genetic findings have been produced in the field of type 2 diabetes. Some evidence has suggested that mature β cell under long-term metabolic stress could de-differentiate into pre-endocrine cells and re-differentiate into α and PP endocrine cells. Several key factors were reported with genetic modified animal models in the past two years. A novel adipokine, Asprosin was found to control insulin resistance and food intake in both humans and mice. Additionally, researchers reported that gut microbiota was associated with the development of type 2 diabetes, and a few bacteria or certain enterotype could be valuable in the prediction of prevention and clinical intervention for diabetes. The genetic composition for missing heritability of type 2 diabetes and obesity was revealed with the next-generation sequencing strategy. Importantly, scientists at home and abroad made a significant progress in the field during the past few years, which should be reviewed here. (Chin J Endocrinol Metab, 2018, 34: 605-609)
ABSTRACT
Este artículo presenta evidencias empíricas y elementos conceptuales para construir la noción de "gaycidad", entendida como una experiencia social distinguible de la experiencia social homosexual. La hipótesis principal sostiene que la gaycidad es heredera de procesos de des-diferenciación social que posibilitan procesos diferenciadores al interior del mundo gay. Si bien está referida a la ciudad argentina de Buenos Aires, aporta reflexiones tendientes a la comparación con otros grandes centros metropolitanos de la región latinoamericana.
Este artigo apresenta evidências empíricas e elementos conceituais para construir a noção de "gaycidade", entendida como uma experiência social distinta da experiência social homossexual. A hipótese principal sustenta que a "gaycidade" é herdeira de processos de desdiferenciação social que possibilitam processos diferenciadores no interior do mundo gay. Embora esteja referida à cidade argentina de Buenos Aires, contribui com reflexões que tendem à comparação com outros grandes centros metropolitanos da região latino-americana.
This article presents empirical evidence and conceptual elements to develop a notion of 'gayness,' understood as a social experience distinct from the 'homosexual' one. The main hypothesis holds that gayness is heir to de-differentiation processes that, in turn, enable differentiating processes within the gay world. Although referred to the city of Buenos Aires, in Argentina, this reflection is aimed at comparing the case to other large metropolitan centers in Latin America.