Identifying Hepatocellular Carcinoma Driver Genes by Integrative Pathway Crosstalk and Protein Interaction Network

Abstract

In this study, we mined out hepatocellular carcinoma (HCC) driver genes from MEDLINE literatures by bioinformatics methods of pathway crosstalk and protein interaction network. Furthermore, the relationship between driver genes and their clinicopathological characteristics, as well as classification effectiveness was verified in the public databases. We identified 560 human genes reported to be associated with HCC in 1074 published articles. Functional analysis revealed that biological processes and biochemical pathways relating to tumor pathogenesis, cancer disease, tumor cell molecule, and hepatic disease were enriched in these genes. Pathway crosstalk analysis indicated that significant pathways could be divided into three modules: cancer disease, virus infection, and tumor signaling pathway. The HCC-related protein-protein interaction network comprised 10,212 nodes, and 56,400 edges were mined out to identify 18 modules corresponding to 14 driver genes. We verified that these 14 driver genes have high classification effectiveness to distinguish cancer samples from normal samples and the classification effectiveness was better than that of randomly selected genes. Present study provided pathway crosstalk and protein interaction network for understanding potential tumorigenesis genes underlying HCC. The 14 driver genes identified from this study are of great translational value in HCC diagnosis and treatment, as well as in clinical study on the pathogenesis of HCC.

System-Wide Pollution of Biomedical Data: Consequence of the Search for Hub Genes of Hepatocellular Carcinoma Without Spatiotemporal Consideration

“…This shows we have found many more key genes than the literature and reinforces the concern that some conclusions about the role and functional significance of these proteins may not be robust. Recently, 560 genes associated with HCC were extracted from 1074 published articles [ 92 ] and another 1509 genes from biobanks [ 93 ]. Both groups presented a comprehensive analysis to select driver [ 92 ] and carbon metabolism genes [ 93 ].…”

“…Recently, 560 genes associated with HCC were extracted from 1074 published articles [ 92 ] and another 1509 genes from biobanks [ 93 ]. Both groups presented a comprehensive analysis to select driver [ 92 ] and carbon metabolism genes [ 93 ]. The different purposes of these studies did not lead to a search for hub genes; however, even though the genomic datasets were well populated, 208 hub genes is an unexpectedly large number.…”

Construction and Analysis of Protein-Protein Interaction Network of Non-Alcoholic Fatty Liver Disease

“…PPI networks are widely accepted for their valuable contribution to the identification of candidate disease-related proteins in several diseases such as hepatocellular carcinoma, blood-cell targeting autoimmune diseases, breast cancer, etc [10, 39, 40]. In the present study, a topological analysis of the NAFLD Interactome was conducted by applying two different approaches (as presented throughout the Methods section), thusly a total of 77 candidate NAFLD-related proteins were identified .…”

“…3, 6 th Cluster-magenta nodes). [10,39,40]. In the present study, a topological analysis of the NAFLD Interactome was conducted by applying two different approaches (as presented throughout the Methods section), thusly a total of 77 candidate NAFLD-related proteins were identified.…”

Inflammatory Mechanisms of HCC Development

“…The analyses conducted at the system biology level are proving to be of great interest. Recently, Chen and colleagues [29] carried out a bioinformatic analysis of 1074 published articles that led to the identification of 560 human genes associated with HCC. These genes are involved in gene expression, protein catabolism, DNA methylation or transcription.…”