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六种基因对人类肝细胞癌的诊断和预后具有潜在价值。

Promising diagnostic and prognostic value of six genes in human hepatocellular carcinoma.

作者信息

Zhang Guanqi, Kang Zhengchun, Mei Hongliang, Huang Zhiyuan, Li Hanjun

机构信息

Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, P.R. China.

Department of Colorectal Surgery, Changhai Hospital, Navy Medical University Shanghai 200433, P.R. China.

出版信息

Am J Transl Res. 2020 Apr 15;12(4):1239-1254. eCollection 2020.

Abstract

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Ample data have been reported to unravel the carcinogenesis over the past decades. Although pinpointing the cause of the HCC is challenging, this in and of itself may not be an insuperable problem. Indeed, the emergence of novel molecular targets has given rise to targeted therapy for HCC. Compared to traditional treatments, drugs with molecularly targeted agents are considered an optimal way to treat HCC. However, targeted approaches are currently limited among HCC patients. In our work, we explored more potential genes for targeted treatment of HCC. Initially, differentially expressed genes (DEGs) were identified in gene expression profiling interactive analysis (GEPIA) and NetworkAnalyst. Subsequently, 10 key genes were selected through enrichment analysis and PPI network construction. Based on the GEPIA and Oncomine databases, six upregulated genes were selected. High protein expression of these six genes were confirmed through the Human Protein Atlas database. In addition, these six genes were associated with unfavorable overall survival and progression-free survival based on Kaplan-Meier plotter bioinformatics. Moreover, gene expression was closely related to the tumor stages and pathological grades, as determined with UALCAN. More importantly, PTTG1, UBE2C, and ZWINT were identified as potential targets of anti-cancer drugs using cBioPortal. qPCR and western blot assays were used to show the high expression levels of the latter three genes in HCC cell lines. Collectively, these findings are expected to provide a theoretical basis for and give novel insights into clinical research of HCC.

摘要

肝细胞癌(HCC)是原发性肝癌最常见的类型。在过去几十年里,已有大量数据报道用于揭示其致癌机制。尽管确定HCC的病因具有挑战性,但这本身可能并非一个无法解决的问题。事实上,新型分子靶点的出现催生了针对HCC的靶向治疗。与传统治疗方法相比,使用分子靶向药物被认为是治疗HCC的最佳方式。然而,目前靶向治疗方法在HCC患者中的应用有限。在我们的研究中,我们探索了更多用于HCC靶向治疗的潜在基因。首先,在基因表达谱交互式分析(GEPIA)和NetworkAnalyst中鉴定出差异表达基因(DEG)。随后,通过富集分析和蛋白质-蛋白质相互作用(PPI)网络构建选择了10个关键基因。基于GEPIA和Oncomine数据库,选择了6个上调基因。通过人类蛋白质图谱数据库证实了这6个基因的高蛋白质表达。此外,基于Kaplan-Meier绘图仪生物信息学,这6个基因与不良的总生存期和无进展生存期相关。而且,通过UALCAN确定基因表达与肿瘤分期和病理分级密切相关。更重要的是,使用cBioPortal将垂体瘤转化基因1(PTTG1)、泛素结合酶E2C(UBE2C)和ZW10丝氨酸/苏氨酸激酶相互作用蛋白(ZWINT)鉴定为抗癌药物的潜在靶点。采用定量聚合酶链反应(qPCR)和蛋白质免疫印迹法检测后三个基因在HCC细胞系中的高表达水平。总的来说,这些发现有望为HCC的临床研究提供理论依据并带来新的见解。

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