Abstract
BackgroundIn 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.MethodsWe 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.ResultsThere 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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1472-6882-14-371) contains supplementary material, which is available to authorized users.
Highlights
In traditional Chinese medicine (TCM) clinical practice, ZHENG helps to understand the human homeostasis and guide individualized treatment
All the outpatients were diagnosed by attending TCM physicians at the first time and identified by three chief TCM physicians, who were consistently diagnosed as dampness-heat accumulation syndrome (DHAS) or liver depression and spleen deficiency syndrome (LDSDS) by all of the physicians were enrolled in this study [10,11]
Identification of core genes of DHAS and LDSDS in hepatitis B-caused cirrhosis (HBC) We analyze the differentially expressed genes (DEGs) of DHAS and LDSDS from the microarrays data
Summary
In traditional Chinese medicine (TCM) clinical practice, ZHENG ( known as TCM syndrome) helps to understand the human homeostasis and guide individualized treatment. Since HBV replication may persist after the development of chronic hepatitis B (CHB) [2], hepatitis B-caused cirrhosis (HBC) is happen. Traditional Chinese medicine (TCM) is extensively used for treatment of liver disease in China, with the great advantages in early intervention, combination therapies, personalized medicine, etc. TCM treatment is based on ZHENG ( known as TCM syndrome) differentiation, namely, discerning patterns of imbalances within the body and between the body and the environment by the analysis of symptoms and signs of patients. The phenotype-oriented diagnosis and therapy in TCM needs to be objective and quantified evaluation for the inheritance [5]
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