title: A systems biology-based classifier for hepatocellular carcinoma diagnosis.
abstract: OBJECTIVE
  The diagnosis of hepatocellular carcinoma (HCC) in the early stage is crucial to the application of curative treatments which are the only hope for increasing the life expectancy of patients. Recently, several large-scale studies have shed light on this problem through analysis of gene expression profiles to identify markers correlated with HCC progression. However, those marker sets shared few genes in common and were poorly validated using independent data. Therefore, we developed a systems biology based classifier by combining the differential gene expression with topological features of human protein interaction networks to enhance the ability of HCC diagnosis.
  
  
  RESULTS
  In the Oncomine platform, genes differentially expressed in HCC tissues relative to their corresponding normal tissues were filtered by a corrected Q value cut-off and Concept filters. The identified genes that are common to different microarray datasets were chosen as the candidate markers. Then, their networks were analyzed by GeneGO Meta-Core software and the hub genes were chosen. After that, an HCC diagnostic classifier was constructed by Partial Least Squares modeling based on the microarray gene expression data of the hub genes. Validations of diagnostic performance showed that this classifier had high predictive accuracy (85.88∼92.71%) and area under ROC curve (approximating 1.0), and that the network topological features integrated into this classifier contribute greatly to improving the predictive performance. Furthermore, it has been demonstrated that this modeling strategy is not only applicable to HCC, but also to other cancers.
  
  
  CONCLUSIONS
  Our analysis suggests that the systems biology-based classifier that combines the differential gene expression and topological features of human protein interaction network may enhance the diagnostic performance of HCC classifier.
authors.affiliation: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Yanqiong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shaochuang
authors.initials: S
authors.lastname: Wang
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Jiyang
authors.initials: J
authors.lastname: Zhnag
authors.forename: Dianhua
authors.initials: D
authors.lastname: Gu
authors.forename: Yunping
authors.initials: Y
authors.lastname: Zhu
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D060066:Protein Interaction Maps; D049490:Systems Biology
chemical_list: D014408:Biomarkers, Tumor