title: Study of ZHENG differentiation in hepatitis B-caused cirrhosis: a transcriptional profiling analysis.
abstract: BACKGROUND
  In traditional Chinese medicine (TCM) clinical practice, ZHENG (also known as TCM syndrome) helps to understand the human homeostasis and guide individualized treatment. However, the scientific basis of ZHENG remains unclear due to limitations of current reductionist approaches.
  
  
  METHODS
  We collected the leukocyte samples of three hepatitis B-caused cirrhosis (HBC) patients with dampness-heat accumulation syndrome (DHAS) and three HBC patients with liver depression and spleen deficiency syndrome (LDSDS) for microarray analysis. We generated Gene-Regulatory-Networks (GeneRelNet) from the differentially expressed genes (DEGs) of microarray date. Core genes were validated using anther independent cohort of 40 HBC patients (20 DHAS, 20 LDSDS) with RT-PCR.
  
  
  RESULTS
  There were 2457 mapped genes were differentially expressed between DHAS and LDSDS (Fold change ≥ 2.0, P < 0.05). There were markedly different genes co-expression patterns in DHAS and LDSDS. Furthermore, three differential co-expression genes including purine nucleoside phosphorylase (PNP); aquaporin 7 (AQP7) and proteasome 26S subunit, non-ATPase 2 (PSMD2) were screened by GeneRelNets, and their mRNA expressions were further validated by real time RT-PCR. The results were consistent with microarray. The PNP (P = 0.007), AQP7 (P = 0.038) and PSMD2 (P = 0.009) mRNA expression is significant difference between DHAS and LDSDS using the non-parametric test. Furthermore, we constructed an mRNA panel of PNP, AQP7 and PSMD2 (PAP panel) by logistic regression model, and evaluated the PAP panel to distinguish DHAS from LDSDS by area under the receiver operating characteristic curve (AUC) analysis, which showed a higher accuracy (AUC = 0.835). Gene ontology (GO) analysis indicated that the DHAS is most likely related to system process while the functions overrepresented by LDSDS most related to the response to stimulus.
  
  
  CONCLUSIONS
  This study suggested that there are particular transcriptional profiles, genes co-expressions patterns and functional properties of DHAS and LDSDS, and PNP, AQP7, and PSMD2 may be involved in ZHENG differentiation of DHAS and LDSDS in HBC.
authors.forename: Yi-Yu
authors.initials: YY
authors.lastname: Lu
authors.forename: Qi-Long
authors.initials: QL
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Guan
authors.forename: Zhi-Zhong
authors.initials: ZZ
authors.lastname: Guo
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yi-Yang
authors.initials: YY
authors.lastname: Hu
authors.affiliation: Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong, Shanghai 201203, China. shibingsu07@163.com.
authors.forename: Shi-Bing
authors.initials: SB
authors.lastname: Su
mesh_terms: D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006509:Hepatitis B / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D008297:Male; D008516:Medicine, Chinese Traditional / Q000379:methods*; D008875:Middle Aged; D012372:ROC Curve; D059467:Transcriptome