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2016 ; 12
(5
): 3285-3295
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Systematic tracking of disrupted modules identifies significant genes and
pathways in hepatocellular carcinoma
#MMPMID27899995
Zhang MH
; Shen QH
; Qin ZM
; Wang QL
; Chen X
Oncol Lett
2016[Nov]; 12
(5
): 3285-3295
PMID27899995
show ga
The objective of the present study is to identify significant genes and pathways
associated with hepatocellular carcinoma (HCC) by systematically tracking the
dysregulated modules of re-weighted protein-protein interaction (PPI) networks.
Firstly, normal and HCC PPI networks were inferred and re-weighted based on
Pearson correlation coefficient. Next, modules in the PPI networks were explored
by a clique-merging algorithm, and disrupted modules were identified utilizing a
maximum weight bipartite matching in non-increasing order. Then, the gene
compositions of the disrupted modules were studied and compared with
differentially expressed (DE) genes, and pathway enrichment analysis for these
genes was performed based on Expression Analysis Systematic Explorer. Finally,
validations of significant genes in HCC were conducted using reverse
transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The
present study evaluated 394 disrupted module pairs, which comprised 236
dysregulated genes. When the dysregulated genes were compared with 211 DE genes,
a total of 26 common genes [including phospholipase C beta 1, cytochrome P450
(CYP) 2C8 and CYP2B6] were obtained. Furthermore, 6 of these 26 common genes were
validated by RT-qPCR. Pathway enrichment analysis of dysregulated genes
demonstrated that neuroactive ligand-receptor interaction, purine and drug
metabolism, and metabolism of xenobiotics mediated by CYP were significantly
disrupted pathways. In conclusion, the present study greatly improved the
understanding of HCC in a systematic manner and provided potential biomarkers for
early detection and novel therapeutic methods.
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