Ehsani Ardakani Mohammad Javad, Safaei Akram, Arefi Oskouie Afsaneh, Haghparast Hesam, Haghazali Mehrdad, Mohaghegh Shalmani Hamid, Peyvandi Hassan, Naderi Nosratollah, Zali Mohammad Reza
Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Gastroenterol Hepatol Bed Bench. 2016 Dec;9(Suppl1):S14-S22.
In the current study, we analysised only the articles that investigate serum proteome profile of cirrhosis patients or HCC patients versus healthy controls.
Increased understanding of cancer biology has enabled identification of molecular events that lead to the discovery of numerous potential biomarkers in diseases. Protein-protein interaction networks is one of aspect that could elevate the understanding level of molecular events and protein connections that lead to the identification of genes and proteins associated with diseases.
Gene expression data, including 63 gene or protein names for hepatocellular carcinoma and 29 gene or protein names for cirrhosis, were extracted from a number of previous investigations. The networks of related differentially expressed genes were explored using Cytoscape and the PPI analysis methods such as MCODE and ClueGO. Centrality and cluster screening identified hub genes, including APOE, TTR, CLU, and APOA1 in cirrhosis.
CLU and APOE belong to the regulation of positive regulation of neurofibrillary tangle assembly. HP and APOE involved in cellular oxidant detoxification. C4B and C4BP belong to the complement activation, classical pathway and acute inflammation response pathway. Also, it was reported TTR, TFRC, VWF, CLU, A2M, APOA1, CKAP5, ZNF648, CASP8, and HSP27 as hubs in HCC. In HCC, these include A2M that are corresponding to platelet degranulation, humoral immune response, and negative regulation of immune effector process. CLU belong to the reverse cholesterol transport, platelet degranulation and human immune response. APOA1 corresponds to the reverse cholesterol transport, platelet degranulation and humoral immune response, as well as negative regulation of immune effector process pathway.
In conclusion, this study suggests that there is a common molecular relationship between cirrhosis and hepatocellular cancer that may help with identification of target molecules for early treatment that is essential in cancer therapy.
在本研究中,我们仅分析了那些研究肝硬化患者或肝癌患者与健康对照者血清蛋白质组图谱的文章。
对癌症生物学的深入了解使得能够识别导致在疾病中发现众多潜在生物标志物的分子事件。蛋白质-蛋白质相互作用网络是能够提升对导致识别与疾病相关基因和蛋白质的分子事件及蛋白质连接的理解水平的一个方面。
从先前的一些研究中提取基因表达数据,包括63个肝细胞癌的基因或蛋白质名称以及29个肝硬化的基因或蛋白质名称。使用Cytoscape以及诸如MCODE和ClueGO等蛋白质-蛋白质相互作用分析方法探索相关差异表达基因的网络。中心性和聚类筛选确定了枢纽基因,包括肝硬化中的载脂蛋白E(APOE)、甲状腺素转运蛋白(TTR)、簇集蛋白(CLU)和载脂蛋白A1(APOA1)。
CLU和APOE属于神经原纤维缠结组装正调控的调节。HP和APOE参与细胞氧化剂解毒。C4B和C4BP属于补体激活经典途径和急性炎症反应途径。此外,据报道TTR、转铁蛋白受体(TFRC)、血管性血友病因子(VWF)、CLU、α2-巨球蛋白(A2M)、APOA1、细胞骨架相关蛋白5(CKAP5)、锌指蛋白648(ZNF648)、半胱天冬酶8(CASP8)和热休克蛋白27(HSP27)是肝癌中的枢纽基因。在肝癌中,这些包括与血小板脱颗粒、体液免疫反应和免疫效应过程负调控相对应的A2M。CLU属于逆向胆固醇转运、血小板脱颗粒和人类免疫反应。APOA1对应逆向胆固醇转运、血小板脱颗粒和体液免疫反应,以及免疫效应过程途径的负调控。
总之,本研究表明肝硬化和肝细胞癌之间存在共同的分子关系,这可能有助于识别癌症治疗中至关重要的早期治疗靶分子。