BMC Complementary and Alternative Medicine | |
Study of ZHENG differentiation in Hepatitis B-caused cirrhosis: a transcriptional profiling analysis | |
Shi-Bing Su1  Yi-Yang Hu2  Wei Zhang3  Hui Zhang1  Zhi-Zhong Guo1  Yan Guan1  Qi-Long Chen1  Yi-Yu Lu1  | |
[1] Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong, Shanghai 201203, China;Shuguang Hospital, Shanghai University of TCM, Shanghai 201203, China;Longhua Hospital, Shanghai University of TCM, Shanghai 200126, China | |
关键词: Hepatitis B-caused cirrhosis; Gene co-expression; Differentially expressed genes; Transcriptional profiling; ZHENG differentiation; | |
Others : 1086411 DOI : 10.1186/1472-6882-14-371 |
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received in 2013-10-14, accepted in 2014-09-29, 发布年份 2014 | |
【 摘 要 】
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.
【 授权许可】
2014 Lu et al.; licensee BioMed Central Ltd.
【 预 览 】
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【 参考文献 】
- [1]Lavanchy D: Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 2004, 11:97-107.
- [2]Liaw YF, Chu CM: Hepatitis B virus infection. Lancet 2009, 373:582-592.
- [3]Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP: The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 2006, 45:529-538.
- [4]Schütte K, Bornschein J, Malfertheiner P: Hepatocellular carcinoma–epidemiological trends and risk factors. Dig Dis 2009, 27:80-92.
- [5]Su SB, Lu A, Li S, Jia W: Evidence-based ZHENG: a traditional Chinese medicine syndrome. Evid base Compl Alternative Med 2012, 2012:246538. http://www.hindawi.com/journals/ecam/2012/246538/ webcite
- [6]Guo ZZ, Yu SH, Guan Y, Li YY, Lu YY, Zhang H, Su SB: Molecular mechanisms of same TCM syndrome for different diseases and different TCM syndrome for same disease in chronic hepatitis B and liver cirrhosis. Evid base Compl Alternative Med 2012, 2012:120350. http://www.hindawi.com/journals/ecam/2012/120350/ webcite
- [7]Chen QL, Lu YY, Zhang GB, Song YN, Zhou Q-M, Zhang H, Zhang W, Su S-B: Progression from excessive to deficient syndromes in chronic Hepatitis B: a dynamical network analysis of miRNA array data. Evid base Compl Alternative Med 2013, 2013:120350.
- [8]Zhang YX, Wei BH: Standard of clinic diagnosis, syndrome differentiation and assessing curative effect on hepatocirrhosis. Chin J Integrated Trad West Med Gastro-spleen 1994, 14:237-238.
- [9]Association CM: Chronic hepatitis B prevention and treatment guidelines. Chinese J Infect Dis 2001, 19:56-62.
- [10]Zhao Y, Gou XJ, Dai JY, Peng JH, Feng Q, Sun SJ, Cao HJ, Zheng NN, Fang JW, Jiang J, Su SB, Liu P, Hu YY, Zhang YY: Differences in metabolites of different tongue coatings in patients with chronic hepatitis B. Evid base Compl Alternative Med 2013, 2013:204908.
- [11]Sun SJ, Dai JY, Fang JW, Gou XJ, Cao HJ, Zheng NN, Wang Y, Zhang W, Zhang YY, Jia W: Differences of excess and deficiency Zheng in patients with chronic hepatitis B by urinary metabonomics. Evid base Compl Alternative Med 2013, 2013:738245. http://www.hindawi.com/journals/ecam/2013/738245/ webcite
- [12]Gertler R, Rosenberg R, Fuehrer K, Dahm M, Nekarda H, Siewert JR: Detection of circulating tumor cells in blood using an optimized density gradient centrifugation. In Molecular Staging of Cancer. Springer; 2003:149-155.
- [13]Pujana MA, Han JDJ, Starita LM, Stevens KN, Tewari M, Ahn JS, Rennert G, Moreno V, Kirchhoff T, Gold B: Network modeling links breast cancer susceptibility and centrosome dysfunction. Nat Genet 2007, 39:1338-1349.
- [14]Barabási AL, Oltvai ZN: Network biology: understanding the cell's functional organization. Nat Rev Genet 2004, 5:101-113.
- [15]Ravasz E, Somera AL, Mongru DA, Oltvai ZN, Barabási A-L: Hierarchical organization of modularity in metabolic networks. Science 2002, 297:1551-1555.
- [16]Carlson MR, Zhang B, Fang ZX, Mischel PS, Horvath S, Nelson SF: Gene connectivity, function, and sequence conservation: predictions from modular yeast co-expression networks. BMC Genomics 2006, 7:40. BioMed Central Full Text
- [17]Zhu LL, Meng H, Jiang J: Study on TCM syndrome typing of chronic hepatitis B. Chin J Integrated Tradit West Med 2008, 28:20.
- [18]Organization WH: WHO international standard terminologies on traditional medicine in the western pacific region. In Book WHO international standard terminologies on traditional medicine in the western pacific region (Editor ed.^eds.). City: City; 2007.
- [19]Deaciuc IV, Song ZY, McClain CJ: Lessons from large-scale gene profiling of the liver in alcoholic liver disease. Hepatol Res 2005, 31:187-192.
- [20]Hoekstra M, Li Z, Kruijt JK, Eck MV, Berkel TJV, Kuiper J: The expression level of non-alcoholic fatty liver disease-related gene PNPLA3 in hepatocytes is highly influenced by hepatic lipid status. J Hepatol 2010, 52:244-251.
- [21]Branch AD, Walewski JL: The coming impact of gene expression profiling on the diagnosis and treatment of HCV-associated liver disease. Antiviral Res 2001, 52:173-179.
- [22]Kurokawa Y, Matoba R, Takemasa I, Nakamori S, Tsujie M, Nagano H, Dono K, Umeshita K, Sakon M, Ueno N: Molecular features of non-B, non-C hepatocellular carcinoma: a PCR-array gene expression profiling study. J Hepatol 2003, 39:1004-1012.
- [23]Trolet J, Hupé P, Huon I, Lebigot I, Decraene C, Delattre O, Sastre-Garau X, Saule S, Thiéry J-P, Plancher C: Genomic profiling and identification of high-risk uveal melanoma by array CGH analysis of primary tumors and liver metastases. Invest Ophthalmol Vis Sci 2009, 50:2572-2580.
- [24]Buriani A, Garcia Bermejo ML, Bosisio E, Xu Q, Li H, Dong X, Simmonds MSJ, Carrara M, Tejedor N, Lucio-Cazana J, Hylands PJ: Omic techniques in systems biology approaches to traditional Chinese medicine research: Present and future. J Ethnopharmacol 2012, 140:535-544.
- [25]Ohuchi T, Tada K, Akamatsu K: Endogenous ET-1 contributes to liver injury induced by galactosamine and endotoxin in isolated perfused rat liver. Am J Physiol Gastrointest Liver Physiol 1995, 31:G997.
- [26]Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S: The current state of serum biomarkers of hepatotoxicity. Toxicology 2008, 245:194-205.
- [27]Hara-Chikuma M, Sohara E, Rai T, Ikawa M, Okabe M, Sasaki S, Uchida S, Verkman A: Progressive adipocyte hypertrophy in aquaporin-7-deficient mice adipocyte glycerol permeability as a novel regulator of fat accumulation. J Biol Chem 2005, 280:15493-15496.
- [28]Wan DF, Gong Y, Qin WX, Zhang PP, Li JJ, Wei L, Zhou XM, Li HN, Qiu XK, Zhong F: Large-scale cDNA transfection screening for genes related to cancer development and progression. Proc Natl Acad Sci U S A 2004, 101:15724-15729.
- [29]Yang CJ, Liu HW, Wang LC: Study on the differential gene expressions of chronic hepatitis B patients of gan depression pi deficiency syndrome and pi-wei damp-heat syndrome. Chin J Integrated Tradit West Med 2012, 32:1032-1037.
- [30]Liu SN, Tao XP, Wang RB: Study on Chinese syndromes developing rules of chronic hepatitis B. Chin J Trad Med Sci Technol 2008, 3:002.
- [31]Li XH, Li JJ, Liu YY, Chen JX: Central neurobiological mechanism of liver depression and spleen deficiency syndrome based on chronic stress: a review. J Chinese Int Medicine 2012, 10:1.
- [32]Yue LF, Ding J, Chen JX, Yue GX, Liang Y, Huo SK, Li JJ: Establishment and review of rat model of syndrome of liver depression with spleen insufficiency. J Beijing University of Trad Chinese Med 2008, 6:396-400.