Evaluation of liver cirrhosis and hepatocellular carcinoma using Protein-Protein Interaction Networks

Mohammad Javad Ehsani Ardakani; Akram Safaei; Afsaneh Arefi Oskouie; Hesam Haghparast; Mehrdad Haghazali; Hamid Mohaghegh Shalmani; Hassan Peyvandi; Nosratollah Naderi; Mohammad Reza Zali

Evaluation of liver cirrhosis and hepatocellular carcinoma using Protein-Protein Interaction Networks

Gastroenterol Hepatol Bed Bench. 2016 Dec;9(Suppl1):S14-S22.

Authors

Mohammad Javad Ehsani Ardakani¹, Akram Safaei², Afsaneh Arefi Oskouie³, Hesam Haghparast⁴, Mehrdad Haghazali⁵, Hamid Mohaghegh Shalmani⁴, Hassan Peyvandi⁶, Nosratollah Naderi⁴, Mohammad Reza Zali¹

Affiliations

¹ Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
² Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
³ Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁴ Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁵ Behbood Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁶ Hearing Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

PMID: 28224023
PMCID: PMC5310795

Abstract

Aim: In the current study, we analysised only the articles that investigate serum proteome profile of cirrhosis patients or HCC patients versus healthy controls.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Cirrhosis; Gene ontology; Hepatocellular carcinoma; Protein-Protein Interaction Network.