Viral Hepatitis
Copyright ©2008 The WJG Press and Baishideng.
World J Gastroenterol. Apr 7, 2008; 14(13): 2010-2022
Published online Apr 7, 2008. doi: 10.3748/wjg.14.2010
Table 1 Expression profiles of marker genes with statistically significant changes during fibrosis progression
Functional categoryDescriptionGene nameExpression at F1GroupExpression ratio
SerialType
F2/F1F3/F2F4/F3
ECM (or other HSC marker)DecorinDCN217.621.211.11.111
Matrix metalloproteinase 2MMP211.721.511.20.921
Hyaluronan-mediated motility receptorHMMR1.222.610.61.131
Lysyl oxidaseLOX1.021.411.20.941
Lysyl oxidase-like 1LOXL10.821.811.41.051
Tropomyosin 1TPM13521.811.51.161
PrionPRNP19.431.210.71.071
Collagen, type I, alpha 1COL1A116.221.32.210.681
Collagen type III alpha 1COL3A1143.921.31.510.891
Collagen type alpha 1COL4A116.821.31.910.6101
HumicanLUM22.821.22.010.9111
SialoproteinSPP113.221.22.211.4121
Glypican 3GPC323.521.82.511.0131
Proline 4-hydroxylase, alpha polypeptide IP4HA13411.10.421.2141
Insignificant change: MGP, BGN, TAGLN, LGALS1, EDG2, EDG5, TNNT2
Inflammation (or apoptosis)LysozymeLYZ185.322.110.81.0152
TGF betaTGFB151.931.510.80.9161
TGF beta 3TGFB33.331.410.90.9173
TNFTNF2.631.710.61.2183
Natural killer cell proteinase 1GZMB1.731.610.51.1191
IL1 betaIL1B2.631.510.71.1203
Hemopoietic cell kinaseHCK22.431.310.60.9214
Interleukin 6 receptorIL6R142.910.90.721.0223
BCL2-related ovarian killerBOK205.910.90.721.1235
Caspase 2CASP21.311.20.720.8245
Chymase 1, mast cellCMA10.220.71.82.21256
Insignificant change: LTBP1, LBP, TNFRSF1B, DEFB1, IL1RN, S100A8, BRIC3, CARD12, CASP1, CASP4, CASP8, PAWR, CD19, CD3Z, MS4A1, CD37, TRA@
Growth factorGrowth hormone receptorGHR102.310.820.90.9264
IGF1IGF156.510.90.721.1271
Insignificant change: PTN, FST, PRLR
Insulin/ Wnt signalCyclin D1CCND1190.621.711.01.0285
Forkhead box M1FOXM10.633.710.81.1294
Gap junction protein, alpha 1, 43 kDa (connexin 43)GJA1432.410.51.0305
V-akt murine thymoma viral oncogene homolog 1AKT177.610.90.921.0314
V-akt murine thymoma viral oncogene homolog 2AKT259.610.90.720.8327
Catenin (cadherin-associated protein), beta 1, 88 kDaCTNNB115911.10.721.0335
Catenin, beta interacting protein 1CTNNBIP12411.10.720.8345
Glycogen synthase kinase 3 betaGSK3B44.111.10.820.8355
Dishevelled, dsh homolog 1 (Drosophila)DVL112.211.10.720.9367
Membrane-bound transcription factor peptidase, site 1MBTPS172.410.90.721.0377
Membrane-bound transcription factor peptidase, site 2MBTPS213.210.90.721.0387
Tribbles homolog 3 (Drosophila)TRIB318.411.10.90.42397
Insignificant change: GSK3A, INSIG1, INSIG2, PRKCB1, PRKCD
Others signalRegucalcin (senescence marker protein-30)RGN697.810.90.80.82564
Insignificant change: DAB2, PMP22, S100A10, LCN2
Transcription factorsCCAAT/enhancer binding protein (C/EBP), alphaCEBPA352.210.721.20.7404
Retinoid X receptor, alphaRXRA409.610.721.00.8414
Hepatocyte nuclear factor 4, alphaHNF4A708.710.721.10.9424
Transcription factor 1 (HNF1)TCF126.710.820.90.8434
Nuclear receptor subfamily 0, group B, member 2NR0B2166.710.720.90.8444
Peroxisome proliferative activated receptor, alphaPPARA62.910.720.80.9454
Inhibitor of DNA binding 1 (splice variation)ID1463.431.610.51.4461
AE binding protein 1AEBP124.621.411.21.0474
Nuclear receptor subfamily 1, group H, member 2NR1H2 (LXRB)911.20.721.0487
Nuclear receptor subfamily 1, group H, member 3NR1H3 (LXRA)27.811.00.720.8497
Nuclear receptor subfamily 1, group H, member 4NR1H4 (FXR)10711.00.720.9507
c/EBPbetaCEBPB274.310.90.720.9512
Upstream transcription factor 2, c-fos interactingUSF2323.710.90.720.9524
Estrogen-related receptor alphaESRRA79.611.20.620.8537
C-metMET73.511.00.721.1543
Upstream transcription factor 1USF130.811.00.90.82554
Insignificant change: ONECUT1, JUNB, NR3C1, PPARG, PPARGC1B, PPARGC1A, SREBF2, FHL2
TransporterSolute carrier family 6, member 6SLC6A63.732.510.61.0575
Solute carrier family 7, member 1SLC7A10.932.310.71.3585
Solute carrier family 38, member 2 Alanine-trasnporter)SLC38A268.631.310.61.0595
Solute carrier family 25 member 15SLC25A1585.711.10.720.9605
Solute carrier family 7, member 7SLC7A77.111.10.621.0615
Solute carrier family 17 (sodium phosphate), member 1SLC17A123.610.90.721.0624
Insignificant change: SLC38A3, ABCB1, SLC15A4
RedoxCatalaseCAT1977.710.820.91.0634
Paraoxonase 1PON1191.110.80.720.9644
Blood coagulationCoagulation factor XF10187.510.821.00.9654
AngiotensinogenAGT1958.410.821.01.0664
Fibrinogen, A alpha polypeptideFGA8337.510.621.00.9674
PlasminogenPLG6156.110.820.81.0684
Pai ISERPINE111.630.92.910.5691
Lipid metabolismAcyl-Coenzyme A oxidase 2, branched chainACOX2122.210.820.90.9704
L-3-hydroxyacyl-Coenzyme A dehydrogenase, short chainHADHSC139.810.820.90.9714
Acyl-CoA synthetase long-chain family member 1ACSL12800.810.820.90.9724
Acyl-Coenzyme A oxidase 1, palmitoylACOX1357.710.720.91.0734
Carnitine O-octanoyltransferaseCROT10.310.720.81.1744
2,4-dienoyl CoA reductase 2, peroxisomalDECR2135.210.820.90.9754
Acetyl-Coenzyme A acyltransferase 2ACAA21167.710.820.81.1764
Acetyl-Coenzyme A acetyltransferase 1ACAT1714.210.721.10.8774
Acyl-CoA synthetase long-chain family member 5ACSL557.310.820.91.0784
Dodecenoyl-Coenzyme A delta isomeraseDCI327.210.920.80.9794
Enoyl Coenzyme A hydratase, short chain, 1, mitochondrialECHS1324.310.721.00.9804
Hydroxyacyl-Coenzyme A dehydrogenase, type IIHADH2422.510.720.90.9814
Hydroxyacyl-Coenzyme A dehydrogenase, beta subunitHADHB398.810.820.91.1824
Lipase, hepaticLIPC561.510.521.50.9834
Hydroxyacyl-Coenzyme A dehydrogenase, alpha subunitHADHA103.210.90.921.0844
Palmitoyl-protein thioesterase 1PPT182.111.00.820.8854
Fatty acid synthaseFASN105.330.81.810.6864
Peroxisomal D3, D2-enoyl-CoA isomerasePECI292.810.80.80.82874
Acyl-CoA synthetase long-chain family member 4ACSL45.821.11.42.31884
Insignificant change: BHHADH, ACAA1, CPT1A, ACADM, ACACA, CPT2
Steroid (or drug) metabolismAldo-keto reductase family 1, member D1AKR1D1248.310.620.80.6894
HMT1 hnRNP methyltransferase-like 2HRMT1L26.610.821.00.8904
Hydroxysteroid (11-beta) dehydrogenase 1HSD11B11064.610.720.80.8914
Hydroxysteroid (17-beta) dehydrogenase 4HSD17B466.710.820.90.9924
Steroid-5-alpha-reductase, alpha polypeptide 1SRD5A174.310.720.80.9934
UDP glycosyltransferase 2 family, polypeptide B7UGT2B7530.310.820.80.9944
Sulfotransferase family 1E, estrogen-preferring, member 1SULT1E152.810.520.51.4957
Aldo-keto reductase family 1, member C4AKR1C4137.110.90.621.2964
Hydroxysteroid (17-beta) dehydrogenase 2HSD17B2496.911.00.821.1974
Sulfotransferase family, cytosolic, 2A, member 1SULT2A168910.90.820.9984
Hydroxysteroid (17-beta) dehydrogenase 8HSD17B872.210.70.721.0997
Steroid sulfatase (microsomal), arylsulfatase C, isozyme SSTS10.911.01.00.621004
Emopamil binding protein (sterol isomerase)EBP19711.00.70.721015
Farnesyl-diphosphate farnesyltransferase 1FDFT1252.610.70.90.721025
Insignificant change: HSD17B2, HSD3B1, LCMT1, SULT2A1, HMGCR, DHCR7, CES2
Bile acid metabolismSterol O-acyltransferase 1SOAT19.111.00.820.91035
Alcohol dehydrogenase 1C (class I), gamma polypeptideADH1C312.710.70.621.11045
Alcohol dehydrogenase, iron containing, 1ADHFE1112.710.70.720.81055
Cytochrome P450, family 7, subfamily A, polypeptide 1CYP7A1104.110.70.622.91065
ProstanoidArachidonate 5-lipoxygenase-activating proteinALOX5AP7.921.710.71.01073
Leukotriene B4 receptor 2LTB4R22.511.10.721.01083
Insignificant change: LTA4H, CYSLTR1, CYSLTR2, LTC4S, PPT1
Aromatic amino acid metabolismDopa decarboxylaseDDC51.411.00.820.81094
Monoamine oxidase BMAOB426.610.80.821.01104
Kynurenine 3-monooxygenaseKMO51.711.00.721.01114
KynureninaseKYNU63.310.90.720.81124
Tyrosine aminotransferaseTAT658.210.90.521.31134
GTP cyclohydrolase 1GCH149.610.90.720.91144
Insignificant change: HPD
Sulfur-containing amino acid metabolismMAT2MAT2B111.711.10.721.11153
Cystathionase (cystathionine gamma-lyase)CTH11211.00.721.11163
Cystathionine-beta-synthaseCBS350.411.10.720.91173
Betaine-homocysteine methyltransferaseBHMT1032.111.00.721.01183
Methionine adenosyltransferase I, alphaMAT1A547.611.00.521.11192
Cysteine dioxygenase, type ICDO184.410.90.7211201
Glutamate-cysteine ligase, catalytic subunitGCLC175.911.10.621.11211
Glutathione S-transferase A1GSTA12812.311.00.721.01221
Alanyl (membrane) aminopeptidaseANPEP501.910.90.820.91245
Bile acid Coenzyme A: amino acid N-acyltransferaseBAAT284.411.00.621.01255
Glutathione synthetaseGSS70.111.10.820.81265
Lactate dehydrogenase ALDHA716.310.80.721.01275
Mercaptopyruvate sulfurtransferaseMPST684.310.90.720.91285
Serine dehydrataseSDS440.410.90.421.01295
Methionine adenosyltransferase II, alphaMAT2A122.911.00.90.821305
Insignificant change: GGT1, GSR, MTR, DNMMT1, CSAD, GCLM, LDHB
Energy source amino acid metabolismPhosphoenolpyruvate carboxykinase 2 (mitochondrial)PCK2791.810.820.91.01314
Alanine-glyoxylate aminotransferaseAGXT3352.310.720.91.01324
Alanine-glyoxylate aminotransferase 2AGXT2122.810.620.81.01334
Aldehyde dehydrogenase 2 family (mitochondrial)ALDH22027.710.720.90.91344
Aldehyde dehydrogenase 9 family, member A1ALDH9A1160.910.820.80.91354
Pyruvate kinase, liver and RBCPKLR211.310.621.10.71364
Aldehyde dehydrogenase 3 family, member A2ALDH3A2237.410.90.821.11374
Phosphoenolpyruvate carboxykinase 1 (soluble)PCK13166.811.00.521.21384
Dihydrolipoamide dehydrogenaseDLD72.310.90.820.91394
Glutaminase 2 (liver, mitochondrial)GLS2133.810.80.721.01404
Glutamate-ammonia ligaseGLUL6.211.00.621.21414
Glutamic-oxaloacetic transaminase 1, solubleGOT1388.210.90.720.81424
Glutamic-pyruvate transaminaseGPT298.810.80.621.11434
Pyruvate carboxylasePC27.810.70.720.91444
Phosphoglucomutase 1PGM1218.810.80.821.01454
Pyruvate dehydrogenase kinase, isoenzyme 2PDK22410.90.820.91467
Pyruvate dehydrogenase kinase, isoenzyme 4PDK485.610.70.521.41477
Fumarylacetoacetate hydrolaseFAH85.810.90.90.821484
Malic enzyme 1, NADP (+) -dependent, cytosolicME14.921.01.01.311494
Insignificant change: ALDOA, ASNS, GOT2, MGC33309, PDHB, PDK1
Glucose metabolismPhosphorylase, glycogen; liverPYGL37.210.821.01.01504
Aldolase B, fructose-bisphosphateALDOB13141.810.70.820.91514
Hexokinase 3 (white cell)HK33.311.20.620.91524
Glycogen synthase 2 (liver)GYS2276.610.90.620.91537
Sterol regulatory element binding transcription factor 1SREBF110.621.11.210.91544
Glycerol-3-phosphate dehydrogenase 1 (soluble)GPD1130.810.81.00.821554
Ketohexokinase (fructokinase)KHK411.810.71.00.821564
Glucokinase (hexokinase 4) regulatorGCKR204.810.71.00.821574
Aldolase C, fructose-bisphosphateALDOC36.810.70.90.621584
Insignificant change: GCK, PFKFB1, G6PC, HK2
Urea cycleCarbamoyl-phosphate synthetase 1, mitochondrialCPS11230.810.720.90.91597
Ornithine aminotransferase (gyrate atrophy)OAT94.810.520.61.61607
Insignificant change: OTC
Table 2 Types of samples indicating the number of biopsy specimens
Type of sampleNumber of samples
F1F2F3F4
12513149
22313148
32212148
412694
57454
66443
75455
Table 3 Classification of gene clusters based on serial alteration of gene expression along with the fibrosis progression
F1-F2F2-F3F3-F4
Inflammation
Wound-healing (ECM)
Blood coagulation
Transcription factors (cluster 1)Transcription factors (cluster 2)
Insulin/Wnt signal
Lipid metabolism
Steroid metabolism (cluster 1)Steroid metabolism (cluster 1)
Bile acid metabolism
Energy source AA metabolism (cluster 1)Energy source AA metabolism (cluster 1)
Aromatic AA metabolism
Sulfur-containing AA metabolism
Glucose metabolism (cluster 1)Glucose metabolism (cluster 2)