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基于生物信息学分析鉴定 G6PC 为肝细胞癌的潜在预后生物标志物。

Identification of G6PC as a potential prognostic biomarker in hepatocellular carcinoma based on bioinformatics analysis.

机构信息

Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing, China.

Institute for Viral Hepatitis, Chongqing Medical University, Chongqing, China.

出版信息

Medicine (Baltimore). 2022 Aug 19;101(33):e29548. doi: 10.1097/MD.0000000000029548.

Abstract

Hepatocellular carcinoma (HCC) has high mortality and incidence rates around the world with limited therapeutic options. There is an urgent need for identification of novel therapeutic targets and biomarkers for early diagnosis and predicting patient survival with HCC. Several studies (GSE102083, GSE29722, GSE101685, and GSE112790) from the GEO database in HCC were screened and analyzed by GEO2R, gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were conducted with the Database for Annotation, Visualization and Integrated Discovery. The protein-protein interaction network was plotted and the module analysis was performed using Search Tool for the Retrieval of Inter-acting Genes/Proteins database and Cytoscape. The expression and survival of key genes were identified using UALCAN, Kaplan-Meier Plotter and ONCOMINE online databases, and the immune infiltration level of key genes was analyzed via the Tumor Immune Estimation Resource (TIMER) database. Through database analysis, eight key genes were finally screened out, and the expressions of cyclin-dependent kinase regulatory subunit 2 and glucose-6-phosphatase catalytic (G6PC), which were closely related to the survival of HCC patients, was detected by using UALCAN. Further analysis on the differential expression of G6PC in multiple cancerous tumors and normal tissues revealed low expression in many solid tumors by Oncomine and TIMER. In addition, Kaplan-Meier plotter and UALCAN database analysis to access diseases prognosis suggested that low expression of G6PC was significantly associated with poor overall survival in HCC patients. Finally, TIMER database analysis showed a significant negative correlation between G6PC and infiltration levels of six kinds of immune cells. The somatic copy number alterations of G6PC were associated with B cells, CD8+ T cells, CD4+ T cells, macrophages, dentritic cells and neutrophils. These bioinformatic data identified G6PC as a potential key gene in the diagnosis and prognosis of HCC.

摘要

肝细胞癌(HCC)在全球范围内具有较高的死亡率和发病率,治疗选择有限。因此,迫切需要鉴定新的治疗靶点和生物标志物,以便对 HCC 进行早期诊断和预测患者的生存情况。本研究从 GEO 数据库中筛选了四项关于 HCC 的 GSE102083、GSE29722、GSE101685 和 GSE112790 研究,并使用 GEO2R 进行分析,通过数据库 for Annotation, Visualization and Integrated Discovery 进行基因本体论和京都基因与基因组百科全书富集分析。绘制蛋白质-蛋白质相互作用网络,并使用 Search Tool for the Retrieval of Inter-acting Genes/Proteins 数据库和 Cytoscape 进行模块分析。使用 UALCAN、Kaplan-Meier Plotter 和 ONCOMINE 在线数据库鉴定关键基因的表达和生存情况,并通过 Tumor Immune Estimation Resource (TIMER) 数据库分析关键基因的免疫浸润水平。通过数据库分析,最终筛选出 8 个关键基因,并使用 UALCAN 检测与 HCC 患者生存密切相关的细胞周期蛋白依赖性激酶调节亚基 2 和葡萄糖-6-磷酸酶催化(G6PC)的表达。进一步对 G6PC 在多种癌性肿瘤和正常组织中的差异表达进行分析,发现 Oncomine 和 TIMER 提示 G6PC 在许多实体瘤中低表达。此外,Kaplan-Meier plotter 和 UALCAN 数据库分析疾病预后提示 G6PC 低表达与 HCC 患者总体生存率显著相关。最后,TIMER 数据库分析显示 G6PC 与六种免疫细胞浸润水平呈显著负相关。G6PC 的体细胞拷贝数改变与 B 细胞、CD8+T 细胞、CD4+T 细胞、巨噬细胞、树突状细胞和中性粒细胞有关。这些生物信息学数据将 G6PC 鉴定为 HCC 诊断和预后的潜在关键基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce9/9388022/9139b2b14257/medi-101-e29548-g001.jpg

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