title: Identification of dysfunctional biological pathways and their synergistic mechanism in hepatocellular carcinoma process.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is a lethal and prevalent cancer worldwide. This study was conducted to investigate dysfunctional pathways and their synergistic mechanism in the HCC process.
  
  
  METHODS
  We downloaded transcriptome profiling data (GSE25097) from the Gene Expression Omnibus (GEO) database, including 6 healthy liver samples, 40 cirrhosis samples, 243 adjacent non-tumor samples, and 268 HCC samples. Robust Multi-Array (RMA) in R software was employed to preprocess the downloaded dataset, and Student's t-test (FDR less than 0.001) was performed to identify the differentially expressed genes (DEGs) between 4 sample groups. Then, pathway enrichment analysis (FDR less than 0.05) based on iSubpathwayMiner was performed. Furthermore, we performed collaborative analysis on these pathways through calculating the Jaccard index, and crosstalk networks were constructed and visualized by Cytoscape.
  
  
  RESULTS
  Totally, 4617, 9517, and 12,479 DEGs were identified between healthy liver and cirrhosis samples, cirrhosis and adjacent non-tumor samples, and adjacent non-tumor and HCC samples, respectively. Furthermore, a total of 26 crosstalks involving 13 pathways, 78 crosstalks involving 54 pathways, and 86 crosstalks involving 52 pathways were identified through the DEGs between healthy liver and cirrhosis samples, cirrhosis and adjacent non-tumor samples, and adjacent non-tumor and HCC samples, respectively. Moreover, 5 dysfunctional pathways were found to co-exist in the three processes of HCC. Among them, 3 dysfunctional pathways have collaborative relationship, including Staphylococcus aureus infection, leishmaniasis, and Chagas disease.
  
  
  CONCLUSIONS
  In this study, dysfunctional pathways in the HCC process and crosstalks between these pathways were investigated for the first time, providing new insight into the potential mechanisms of HCC.
authors: Department of Oncology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China. Electronic address: wushenglili@hotmail.com.
authors: Jun
authors: J
authors: Liang
authors: Department of Oncology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China. Electronic address: jinglv1211@yeah.net.
authors: Jing
authors: J
authors: Lv
authors: Department of Oncology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China. Electronic address: ziminliu201311@yeah.net.
authors: Zimin
authors: Z
authors: Liu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D055442:Metabolome; D059467:Transcriptome
keywords: Differentially expressed genes; Hepatocellular carcinoma; Pathway enrichment; Synergistic pathways; Transcriptome profiling