Identification of the association between HMMR expression and progression of hepatocellular carcinoma via construction of a co-expression network
Identification of the association between HMMR expression and progression of hepatocellular carcinoma via construction of a co-expression network
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DOI：
10.3892/ol.2020.11844
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发表时间：
2020-09-01
期刊：
影响因子：
2.9
通讯作者：
Lv, Yufeng
中科院分区：
文献类型：
--
作者：
Lu, Donglan;Bai, Xue;Lv, Yufeng
本研究的目的是确定参与肝细胞癌（HCC）进展的关键基因。根据肝癌发生的多步骤过程理论和加权基因共表达网络分析，利用正常人至慢性肝炎/肝硬化患者和异型增生结节至肝癌患者的基因表达谱，筛选与肝癌进展相关的hub基因。使用独立的数据集验证hub基因与临床表型之间的关联。评价hub基因对HCC的诊断和预后价值。基因集富集分析（GSEA），以探讨枢纽基因的功能。一个与HCC进展正相关的共表达基因模块被鉴定。结合蛋白质-蛋白质相互作用（PPI）网络，共10个共同的枢纽基因共同感兴趣的模块和PPI网络被选为枢纽基因。HMMR基因在肝癌组织中的mRNA和蛋白表达水平均显著上调。HMMR是一种很有前途的HCC诊断生物标志物，也与其进展相关。HMMR的表达与HCC分级、病理分期、肿瘤分期及Ishak评分呈正相关。与临床病理特征相比，HMMR的表达是一个独立的预后因素。HMMR高表达的患者预后较差。GSEA鉴定了6个与癌症相关的代表性基因集。总体而言，HMMR可能在HCC中发挥重要作用，并可能成为HCC诊断和进展的生物标志物。
The aim of the present study was to identify key genes involved in the progression of hepatocellular carcinoma (HCC). According to the theory of the multistep process of hepatocarcinogenesis and weighted gene co-expression network analysis, hub genes associated with the progression of HCC were identified using the gene expression profiles of patients with normal to chronic hepatitis/cirrhosis and dysplastic nodules to HCC. An independent dataset was used to verify the association between hub gene and clinical phenotype. The diagnostic and prognostic value of hub genes regarding HCC were evaluated. Gene set enrichment analysis (GSEA) was performed to explore the function of hub genes. A co-expression gene module positively associated with HCC progression was identified. Combined with a protein-protein interaction (PPI) network, a total of 10 common hub genes common to both the module of interest and the PPI network were selected as hub genes. Hyaluronan mediated motility receptor (HMMR) was selected as the candidate gene and was significantly upregulated in HCC at the mRNA and protein expression levels. HMMR is a promising diagnostic biomarker for HCC, and is also associated with its progression. The expression of HMMR was positively correlated with HCC tumor grade, pathological stage, tumor stage and Ishak score. The expression of HMMR was an independent prognostic factor compared with clinicopathological features. Patients with high expression levels of HMMR exhibited a less favorable prognosis. GSEA identified 6 representative gene sets that were associated with cancer. Overall, HMMR may serve an important role in HCC and may have potential as a biomarker of HCC diagnosis and progression.