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肝细胞癌中多个枢纽基因和通路的鉴定:生物信息学分析。

Identification of Multiple Hub Genes and Pathways in Hepatocellular Carcinoma: A Bioinformatics Analysis.

机构信息

Medical College of Soochow University, Suzhou 215006, China.

General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China.

出版信息

Biomed Res Int. 2021 Jul 12;2021:8849415. doi: 10.1155/2021/8849415. eCollection 2021.

Abstract

Hepatocellular carcinoma (HCC) is a common malignant tumor of the digestive system, and its early asymptomatic characteristic increases the difficulty of diagnosis and treatment. This study is aimed at obtaining some novel biomarkers with diagnostic and prognostic meaning and may find out potential therapeutic targets for HCC. We screen differentially expressed genes (DEGs) from the HCC gene expression profile GSE14520 using GEO2R. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted by using the clusterProfiler software while a protein-protein interaction (PPI) network was performed based on the STRING database. Then, prognosis analysis of hub genes was conducted using The Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to further verify the expression of hub genes and explore the correlation between gene expression and clinicopathological parameters. A total of 1053 DEGs were captured, containing 497 upregulated genes and 556 downregulated genes. GO and KEGG analysis indicated that the downregulated DEGs were mainly enriched in the fatty acid catabolic process while upregulated DEGs were primarily enriched in the cell cycle. Simultaneously, ten hub genes (CYP3A4, UGT1A6, AOX1, UGT1A4, UGT2B15, CDK1, CCNB1, MAD2L1, CCNB2, and CDC20) were identified by the PPI network. Five prognosis-related hub genes (CYP3A4, CDK1, CCNB1, MAD2L1, and CDC20) were uncovered by the survival analysis based on TCGA database. The ten hub genes were further validated by qRT-PCR using samples obtained from our hospital. The prognosis-related hub genes such as CYP3A4, CDK1, CCNB1, MAD2L1, and CDC20 could be considered potential diagnosis biomarkers and prognosis targets for HCC. We also use Oncomine for further verification, and we found CCNB1, CCNB2, CDK1, and CYP3A4 which were highly expressed in HCC. Meanwhile, CCNB1, CCNB2, and CDK1 are highly expressed in almost all cancer types, which may play an important role in cancer. Still, further functional study should be conducted to explore the underlying mechanism and biological effect in the near future.

摘要

肝细胞癌 (HCC) 是消化系统常见的恶性肿瘤,其早期无症状的特点增加了诊断和治疗的难度。本研究旨在获得具有诊断和预后意义的新型生物标志物,并可能为 HCC 找到潜在的治疗靶点。我们使用 GEO2R 从 HCC 基因表达谱 GSE14520 中筛选差异表达基因 (DEGs)。使用 clusterProfiler 软件进行基因本体论 (GO) 分析和京都基因与基因组百科全书 (KEGG) 富集分析,同时基于 STRING 数据库进行蛋白质-蛋白质相互作用 (PPI) 网络分析。然后,使用癌症基因组图谱 (TCGA) 数据库进行关键基因的预后分析。实时定量聚合酶链反应 (qRT-PCR) 进一步验证关键基因的表达,并探讨基因表达与临床病理参数的相关性。共捕获到 1053 个 DEGs,其中 497 个上调基因和 556 个下调基因。GO 和 KEGG 分析表明,下调的 DEGs 主要富集在脂肪酸分解代谢过程中,而上调的 DEGs 主要富集在细胞周期中。同时,通过 PPI 网络鉴定出 10 个关键基因 (CYP3A4、UGT1A6、AOX1、UGT1A4、UGT2B15、CDK1、CCNB1、MAD2L1、CCNB2 和 CDC20)。基于 TCGA 数据库的生存分析发现了 5 个与预后相关的关键基因 (CYP3A4、CDK1、CCNB1、MAD2L1 和 CDC20)。进一步使用我们医院获得的样本通过 qRT-PCR 验证了这 10 个关键基因。CYP3A4、CDK1、CCNB1、MAD2L1 和 CDC20 等预后相关关键基因可作为 HCC 的潜在诊断标志物和预后靶点。我们还使用 Oncomine 进行了进一步验证,发现 CYP3A4、CCNB1、CCNB2、CDK1 在 HCC 中高表达。同时,CCNB1、CCNB2 和 CDK1 在几乎所有癌症类型中均高表达,这可能在癌症中发挥重要作用。然而,为了探讨其潜在机制和生物学效应,在不久的将来仍需要进行进一步的功能研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de7b/8292096/a185a6b87e12/BMRI2021-8849415.001.jpg

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