PRIMARY BILIARY CIRRHOSIS (PBC) COMPARED TO NON-DISEASED LIVER AND PRIMARY SCLEROSING CHOLANGITIS (PSC) ASSOCIATED CIRRHOSIS

Individual genes were categorised according to their involvement in the pathogenic processes of inflammation (Table 1), fibrosis (Table 2), proliferation (Table 3), intracellular signalling and nuclear (Table 4), apoptosis (Table 5), stress response (Table 6). Genes were categorised according to their known major function. Genes uncharacterised or lacking a clear function were not categorised (Table 7). Many of the genes listed could be included in more than one category, so genes were categorised in a hierarchical manner in the following order; (i) intracellular signalling and nuclear, (ii) apoptosis, (iii) inflammation, (iv) proliferation, (v) fibrosis, (vi) stress response/oxidative stress and (vii) uncategorised.

Table 8 lists neural associated genes up-regulated in PBC associated cirrhosis, separate to their inclusion in Tables 1 to 7. Table 9 lists the twenty most down-regulated genes in HCV associated cirrhosis compared to non-diseased liver. Table 10 lists the forty most upregulated genes in PBC associated cirrhosis when compared to non-diseased tissue and when compared to PSC associated cirrhosis. Genes common to two comparisons in each table are marked with asterisks.

Differential gene expression was determined as described in the manuscript, with gene up-regulation of 1.5 fold or greater in PBC associated cirrhosis compared to non-diseased liver or PSC associated cirrhosis shown in Tables 1 to 8 and 10. Signal intensities were converted to a ratio adjusted for background and for housekeeper gene expression.

Categorising genes by pathogenic processes

Table 1 Inflammation Associated Genes

Up-regulation in PBC Compared to Non-Diseased Liver

Ratio

Stromal cell derived factor 1 receptor (SDF-1 receptor; CXCR4)

7.2*

Tyrosine-protein kinase receptor flt3; CD135

6.8*

Myeloid cell nuclear differentiation antigen (MNDA)

5.7*

Interleukin-17 (IL-17)

4.0*

Interleukin-3 (IL-3)

3.6*

Interleukin-5 (IL-5)

3.6*

Interleukin-15 (IL-15)

3.5*

Granulocyte-macrophage colony-stimulating factor (GM-CSF R alpha)

3.1*

Lymphotoxin-beta (LT-beta; LTB)

2.9

Interleukin-13 (IL-13)

2.8

Interleukin-1 alpha (IL-1 alpha; IL1A)

2.7*

Interferon-gamma (IFN-gamma) receptor beta subunit

2.5*

Monocyte chemotactic protein 1 (MCP-1)

2.5

C5a anaphylatoxin receptor (C5AR)

2.3

Interferon consensus sequence-binding protein (ICSBP)

2.2

Interleukin-14 (IL-14)

2.2*

Integrin alpha 6; VLA6; CD49f

2.1

Interleukin-4 (IL-4)

2.0*

Interleukin-7 receptor alpha subunit (IL-7R-alpha; IL7R)

2.0*

Tumor necrosis factor receptor (TNFR) + tumor necrosis factor receptor 2 (TNFR2)

2.0

PAI3; plasminogen activator inhibitor 3 (PLANH3)

2.0

CD40 ligand (CD40-L)

2.0

Integrin alpha 5; VLA5; CD49e

2.0

E-selectin

1.9

HLA class I histocompatibility antigen C-4 alpha subunit

1.9*

Interleukin-2 receptor (CD25) alpha subunit (IL-2 receptor alpha subunit; IL2RA)

1.9

Stromal cell derived factor 1 alpha; Fusin; SDF-1A (CXC4)

1.8

LFA-1 beta subunit; CR3; p150; CD18; Integrin beta 2

1.7

N-formyl-methionyl-leucyl-phenylalanine (FMLP)-related receptor I

1.7

Macrophage colony stimulating factor I receptor (CSF-1-R)

1.7

Tumor necrosis factor (TNF-alpha)

1.7

Clusterin (CLU)

1.6

Interleukin-1 beta (IL-1 ; IL1B)

1.6

Interleukin-2 receptor gamma subunit (IL-2R gamma; IL2RG)

1.5

Interleukin-6 receptor beta subunit (IL-6R-beta)

1.5

Granulocyte colony stimulating factor receptor (GCSF-R)

1.5*

Macrophage migration inhibitory factor (MIF)

1.5

Up-regulated in PBC compared to PSC

 

Interleukin-3 (IL-3)

7.8*

Interleukin-15 (IL-15)

6.5*

Interleukin-17 (IL-17)

3.2*

Interleukin-5 (IL-5)

2.6*

Stromal cell derived factor 1 receptor (SDF-1 receptor; CXCR4)

2.3*

Interleukin-4 (IL-4)

2.2*

Tyrosine-protein kinase receptor flt3; CD135

1.8*

HLA class I histocompatibility antigen C-4 alpha subunit

1.6*

Interferon-gamma (IFN-gamma) receptor beta subunit

1.6*

Interleukin-1 alpha (IL-1 alpha; IL1A)

1.6*

Granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSFR-alpha)

1.6*

Interleukin-7 receptor alpha subunit (IL-7R-alpha; IL7R)

1.6*

Granulocyte colony stimulating factor receptor (GCSF-R)

1.5*

Interleukin-14 (IL-14)

1.5*

Myeloid cell nuclear differentiation antigen (MNDA)

1.5*

 

Table 2 Fibrosis Associated Genes

Up-regulation in PBC Compared to Non-Diseased Liver

Ratio

Connective tissue growth factor (CTGF)

13.6*

Transforming growth factor-beta 3 (TGF-beta3)

12.6*

Platelet-activating factor receptor (PAFR)

5.0

Transforming growth factor beta2 (TGF-beta 2)

2.8

Transforming growth factor-alpha (TGF-alpha)

2.8

Fibroblast growth factor receptor 3 (FGFR3)

2.7*

Thrombin receptor (TR); F2R; PAR1

2.7*

N-sam; fibroblast growth factor receptor 1 (FGFR1); basic fibroblast growth factor receptor (bFGFR)

2.6

Cysteine-rich fibroblast growth factor receptor

2.3

Acidic fibroblast growth factor (aFGF) + heparin-binding growth factor 1 (HBGF-1) + beta-endothelial cell growth factor (ECGF-beta)

2.2*

Platelet-derived growth factor receptor beta subunit (PDGF RB)

2.2

Endothelin receptor type B (EDNRB; ETB)

1.8

Extracellular matrix metalloproteinase inducer (EMMPRIN)

1.7*

Endothelin 2 (ET2)

1.5

Transforming growth factor-beta 1 (TGF-beta 1)

1.5

Up-regulated in PBC compared to PSC

 

Transforming growth factor-beta 3 (TGF-beta3)

2.7*

Connective tissue growth factor (CTGF)

2.5*

Thrombin receptor (TR); F2R; PAR1

2.5*

Fibroblast growth factor receptor 3 (FGFR3)

2.1*

Platelet-activating factor receptor (PAFR)

1.8*

Acidic fibroblast growth factor (aFGF) + heparin-binding growth factor 1 (HBGF-1) + beta-endothelial cell growth factor (ECGF-beta)

1.7*

Extracellular matrix metalloproteinase inducer (EMMPRIN)

1.5*

 

 

Table 3 Regeneration, Growth and Proliferation Associated Genes. Includes Differentiation and Development Associated Genes.

Up-regulation in PBC Compared to Non-Diseased Liver

Ratio

Brain-derived neurotrophic factor (BDNF)/NT-3 growth factor receptor; Trk3

29.4

Wnt-2; int-1

12.6*

Jagged-1 (HJ1)

7.9*

Ret proto-oncogene

7.1*

Patched homolog (PTC)

6.7*

Wnt-13

5.7*

Delta-like protein precursor (DLK)

5.3*

Ataxia telangiectasia (ATM)

4.9*

Neurogenic locus notch protein homolog 1 (Notch-1)

4.7*

Wnt-5a

3.6*

Erb B4 receptor protein-tyrosine kinase

3.5*

Jagged-2 (JAG2)

3.5*

Glial cell line-derived neurotrophic factor (GDNF)

3.4

Notch-4

3.2*

Erb B2 receptor protein-tyrosine kinase

3.1

Notch-2

3.1*

Cyclin-dependent kinase inhibitor 1C (CDKN1C); P57-KIP2

3.0

Insulin-like growth factor binding protein 6 (IGFBP-6)

3.0*

Erythroid differentiation protein (EDF)

2.9

Corticotropin releasing factor receptor 1 (CRF-R; CRF1)

2.7*

Heparin binding growth factor 8 (HBGF-8)

2.5*

Kidney epidermal growth factor (EGF)

2.4*

Insulin-like growth factor binding protein 2 (IGFBP-2)

2.4

Beta Ig-H3 (BIGH3); Kerato-Epithelin

2.2

Calcitonin receptor (CTR; CALCR)

2.2

Erythropoietin receptor (EPOR)

2.2*

Glial growth factor; heregulin-beta3; neuregulin

2.1*

Insulin receptor (INSR)

2.1

Wnt-10b; Wnt-12

2.0

Epidermal growth factor receptor (EGFR)

1.9*

Manic fringe

1.9*

G1/S-specific cyclin D1 (CCND1)

1.9

Insulin-like growth factor I receptor (IGF1R)

1.9

Insulin-like growth factor-binding protein 3 (IGFBP-3)

1.9

Brain-derived neurotrophic factor (BDNF)

1.7

Insulin-like growth factor II receptor (IGFR II)

1.7

Smoothened

1.6*

Cyclin-dependent kinase inhibitor 1 (CDKN1A)

1.6

Glia-derived neurite-promoting factor (GDNPF)

1.6

Hepatocyte growth factor activator (HGF activator)

1.6

Insulin-like growth factor binding protein 1 (IGFBP-1)

1.6

Leukemia inhibitory factor (LIF)

1.6

Hepatocyte growth factor receptor (HGF-SF receptor)

1.6

Placenta growth factors 1 + 2 (PLGF1 + PLGF2 )

1.6

Vascular endothelial growth factor (VEGF)

1.6

Epidermal growth factor receptor substrate 15 (EPS15)

1.5

Lunatic fringe

1.5

Cyclin-dependent kinase inhibitor 3 (CDKN3)

1.5

Insulin-like growth factor binding protein 5 (IGFBP-5)

1.5

Low-affinity nerve growth factor (NGF) receptor (NGFR)

1.5

Up-regulated in PBC compared to PSC

 

Ret proto-oncogene

19.3*

Wnt-13

8.7*

Wnt-5a

6.3*

Patched homolog (PTC)

4.1*

Notch-2

4.0*

Notch-4

3.4*

Ataxia telangiectasia (ATM)

3.0*

Neurogenic locus notch protein homolog 1 (Notch-1)

3.0*

Jagged 1 (HJ1)

2.9*

Neurogenic locus notch protein (Notch)

2.8

Erb B4 receptor protein-tyrosine kinase

2.7*

Jagged-2 (JAG2)

2.6*

Kidney epidermal growth factor (EGF)

2.5*

Smoothened

2.5*

Hepatocyte growth factor receptor (HGF-SF receptor)

2.4

Corticotropin releasing factor receptor 1 (CRF-R; CRF1)

2.2*

Delta-like protein (DLK)

2.0*

Calcitonin receptor (CTR; CALCR)

2.0

Wnt-2; int-1

1.9*

Heparin binding growth factor 8 (HBGF-8)

1.7*

Manic fringe

1.7*

Erythropoietin receptor (EPOR)

1.6*

Insulin-like growth factor binding protein 4 (IGFBP-4)

1.6

Epidermal growth factor receptor (EGFR)

1.5*

Hepatocyte growth factor activator (HGF activator)

1.5

Insulin receptor (INSR)

1.5

Insulin-like growth factor binding protein 6 (IGFBP-6)

1.5*

Table 4 Intracellular Signalling and Nuclear Associated Genes

Up-regulation in PBC Compared to Non-Diseased Liver

Ratio

Synapse associated protein 97 (SAP97); homolog of Drosophila discs large protein isoform 1 (HDLG1)

12.5*

Stem cell protein (SCL, TAL-1)

9.0

Transcription factor LSF

7.4

Neural retina-specific leucine zipper protein (NRL)

6.6

DNA damage repair & recombination protein 52 (Rad52)

6.1*

Proto-oncogene c-jun; transcription factor AP-1

5.9*

c-Src proto-oncogene (SRC1)

4.5*

DNA-dependent protein kinase (DNA-PK) + DNA-PK catalytic subunit (DNA-PKCS)

4.3

Growth arrest & DNA-damage-inducible protein (GADD45)

4.3

Nuclear respiratory factor 1 (NRF1)

4.2

Muscle-specific DNase I-like (DNase1L1; DNL1L); DNase X

4.0

Transcription initiation factor 250-kDa subunit (TAFII250)

4.0*

DNA ligase IV (LIG4)

3.7*

DNA-binding protein inhibitor ID-1

3.4

Rad50

3.3*

PAX3/forkhead transcription factor fusion

3.3

DNA ligase III (LIG3)

2.9*

Transcription factor zinc finger in the multiple endocrine neoplasia 1 locus (ZFM1)

2.9

Helix-loop-helix protein HLH 1R21

2.7*

Ku (p70/p80) subunit

2.6*

Transcription factor IIIC box B-binding subunit

2.6

c-Myb proto-oncogene; c-myb

2.5

Fos-related antigen 1 (Fra-1)

2.5

Purine-rich single-stranded DNA-binding protein alpha (PURA)

2.5

v-ErbA related protein (EAR3)

2.4

Growth arrest & DNA damage inducible protein 153 (GADD153)

2.3*

Transcription factor HTF4

2.3

Transducer of Erb B2 (TOB)

2.3

Ets-related protein tel; ets translocation variant 6 (ETV6)

2.3*

ZFM1 protein alternatively spliced product

2.2

c-Myc purine-binding transcription factor puf

2.1*

GA-binding protein beta-2 subunit (GABP-beta2);

2.1

Guanine nucleotide-binding protein G-s alpha subunit

2.1*

Nuclear factor I (NFI)

2.1*

DNA topoisomerase II alpha (TOP2A)

2.0

Related to receptor tyrosine kinase (RYK)

2.0

Tristetraproline (TTP)

2.0*

Replication protein A 70-kDa subunit (RPA70; REPA1; RF-A)

2.0

Xeroderma pigmentosum group D repair complementing protein (XPD); DNA excission repair protein ERCC2

2.0*

n-Myc proto-oncogene

2.0

DNA polymerase alpha catalytic subunit (POLA)

1.9

Phospholipase C (PLC)

1.9

DNA excision repair protein ERCC1

1.8

Basic transcription element-binding protein 2 (BTEB2)

1.8

Beta-catenin (CTNNB)

1.8

Cellular nucleic acid binding protein (CNBP)

1.8

Xeroderma pigmentosum group C repair complementing protein p58/HHR23B

1.8

c-Myc

1.8

Extracellular signal-regulated kinase 2 (ERK2)

1.7*

GTP-binding protein ras associated with diabetes (Rad1)

1.7

Early growth response protein 1 (hEGR1); transcription factor ETR103

1.6

Putative transcription activator DB1

1.6

Transcriptional repressor NF-X1

1.6*

Transforming protein rhoA H12

1.6

MacMARCKS; MARCKS-related protein (MRP)

1.6

Transcription factor AREB6

1.5

Basic transcription factor 62-kDa subunit (BTF2)

1.5

cAMP-dependent transcription factor ATF-4; DNA-binding protein TAXREB67

1.5

CCAAT-binding transcription factor subunit B (CBF-B)

1.5*

DNA-repair protein XRCC1

1.5

HHR23A; UV excision repair protein Rad23A

1.5*

Paired box homeotic protein (PAX8) isoforms 8A/8B + isoforms 8C/8D

1.5*

Signal transducer and activator of transcription 6 (STAT6)

1.5

Transcriptional activator hSNF2-alpha

1.5

Up-regulated in PBC compared to PSC

 

Transcription initiation factor 250-kDa subunit (TAFII250)

85.5*

Paired box homeotic protein (PAX8) isoforms 8A/8B + isoforms 8C/8D

3.1*

CCAAT-binding transcription factor subunit B (CBF-B)

3.0*

DNA ligase IV (LIG4); polydeoxyribonucleotide synthase

2.9*

Growth arrest & DNA damage inducible protein 153 (GADD153)

2.7*

DNA damage repair & recombination protein 52 (Rad52)

2.6*

DNA-dependent protein kinase (DNA-PK) + DNA-PK catalytic subunit (DNA-PKCS)

2.6

c-Src proto-oncogene (SRC1)

2.4*

Basic transcription element-binding protein 2 (BTEB2)

2.4

Basic transcription factor 62-kDa subunit (BTF2)

2.3*

Synapse-associated protein 97 (SAP97); homolog of Drosophila discs large protein isoform 1 (HDLG1)

2.3*

Muscle-specific DNase I-like (DNase1L1)

2.2

Ets-related protein tel; ets translocation variant 6 (ETV6)

2.1*

Rad50

2.0*

c-Myb proto-oncogene

2.0

HHR23A; UV excision repair protein Rad23A

1.9*

Transcription factor LSF

1.9

Transcriptional repressor NF-X1

1.9*

c-Myc purine-binding transcription factor puf

1.8*

Protein-tyrosine kinase transmembrane receptor ror1

1.8

Proto-oncogene c-jun; transcription factor AP-1

1.8*

DNA ligase III (LIG3)

1.7*

Growth arrest & DNA-damage-inducible protein (GADD45)

1.7

Helix-loop-helix protein HLH 1R21

1.7*

Nuclear factor I (NFI)

1.7*

Extracellular signal-regulated kinase 2 (ERK2)

1.6*

Ku (p70/p80) subunit

1.6*

PAX3/forkhead transcription factor fusion

1.6

Tristetraproline (TTP)

1.6*

Xeroderma pigmentosum group D complementing protein (XPD); DNA excission repair protein ERCC2

1.5*

Guanine nucleotide-binding protein G-s alpha subunit

1.5*

Table 5 Apoptosis Associated Genes

Up-regulated in PBC Compared to Non-Diseased Liver tissue

Ratio

Early response protein NAK1; TR3 orphan receptor

4.1*

Bcl-2 homologous antagonist/killer (BAK)

1.7

Apoptosis regulator bax

1.6

Apoptosis regulator bcl-2

1.6

Caspase-8 (CASP8);

1.5

Secreted apoptosis related protein 1 (SARP-1)

1.5

Up-regulated in PBC compared to PSC

 

Early response protein NAK1; TR3 orphan receptor

2.4*

 

 

Table 6 Stress Response Associated Genes

Up-regulated in PBC Compared to Non-Diseased Liver tissue

Ratio

Glutathione S-transferase M1

4.0

70-kDa heat shock protein 1 (HSP70.1)

3.6*

Dioxin-inducible cytochrome P450 1B1 (CYP1B1)

3.1

Heat shock 90-kDa protein A (HSP90A)

3.1*

Heat shock 27-kDa protein (HSP27); HSPB1

2.9*

Cytosolic superoxide dismutase 1 (SOD-1)

2.2

Glutathione peroxidase (GSHPX1)

2.2

Heat shock protein 60 (HSP60)

1.7

Glutathione S-transferase pi (GSTP1)

1.6*

Up-regulated in PBC compared to PSC

 

Heat shock 27-kDa protein (HSP27); HSPB1

2.6*

70-kDa heat shock protein 1 (HSP70.1; HSPA1)

1.7*

Glutathione S-transferase pi (GSTP1)

1.6*

Heat shock 90-kDa protein A (HSP90A)

1.5*

 

Table 7 Uncategorised Genes

Up-regulated in PBC Compared to Non-Diseased Liver tissue

Ratio

Follistatin

10.7*

Prohibitin (PHB)

6.0*

Follicle stimulating hormone receptor (FSHR); follitropin receptor

6.0*

Prorelaxin H2 (RLN2)

5.5*

Thrombomodulin (THBD; THRM)

4.5*

Frizzled-related FrzB (FRITZ) + FrzB + frezzled (FRE)

4.4*

Cellular retinoic acid-binding protein II (CRABP2)

3.5

Renin-binding protein (RENBP; RNBP)

3.2*

Erythroid differentiation protein (EDF); inhibin beta A subunit; activin beta A subunit

2.9

Ephrin type B receptor 2

2.9

MutL protein homolog

2.9

Thymosin beta-10 (TMSB10; THYB10); PTMB10

2.8

Ephrin type A receptor 3

2.5*

Angiotensin-converting enzyme (ACE)

2.4*

Angiotensin II type 1A receptor

2.4*

Brain-specific tubulin alpha 1 subunit (TUBA1)

2.3

Activator 1 37-kDa subunit; replication factor C 37-kDa subunit (RFC37); RFC4

2.1

Liver glyceraldehyde 3-phosphate dehydrogenase (GAPDH)

2.1

Orphan hormone nuclear receptor

2.1

Tyrosine kinase receptor tie-1

2.0

40S ribosomal protein S9

2.0

60S ribosomal protein L6 (RPL6)

2.0

Ephrin type B receptor 3

2.0

Activin type I receptor

1.8

23-kDa highly basic protein; 60S ribosomal protein L13A (RPL13A)

1.8

Hypoxanthine-guanine phosphoribosyltransferase (HPRT)

1.8*

Prothymosin alpha

1.8

Ubiquitin

1.8

Protein-tyrosine kinase transmembrane receptor ror1

1.8

Serine/threonine-protein kinase receptor R3

1.8

Tyrosine-protein kinase receptor tyro3

1.8

Ubiquitin-conjugating enzyme E2 17-kDa (UBE2A)

1.7

Eph-related receptor tyrosine kinase ligand 1 (EPGL1)

1.7

Ephrin type B receptor 4

1.6

Neurotrophic tyrosine kinase receptor-related 3

1.5

Cytoplasmic beta-actin (ACTB)

1.5

Tumor suppressor LUCA1

1.5

Up-regulated in PBC compared to PSC

 

Prorelaxin H2 (RLN2)

3.8*

Renin-binding protein (RENBP; RNBP)

3.7*

Follicle stimulating hormone receptor (FSHR)

3.6*

Angiotensin II type 1A receptor (AT1AR)

3.4*

Follistatin

3.0*

Thrombomodulin (THBD; THRM)

2.8*

Frizzled-related FrzB (FRITZ) + FrzB + frezzled (FRE)

2.4*

Thymosin beta-10

2.0

Protein tyrosine kinase receptor ror1

1.8

Tyrosine kinase receptor tie-1

1.7

Ephrin type A receptor 3

1.6*

Angiotensin-converting enzyme (ACE)

1.6*

Hypoxanthine-guanine phosphoribosyltransferase (HPRT)

1.6*

Related to receptor tyrosine kinase (RYK)

1.5

Prohibitin (PHB)

1.5*

Table 8 Neural Associated Genes

Up-regulated in PBC Compared to Non-Diseased Liver tissue

Ratio

Brain derived neurotrophic factor (BDNF)/NT-3 growth factors receptor; Trk-3

29.4

Synapse associated protein 97 (SAP97); homolog of Drosophila discs large isoform 1 (HDLG1)

12.5

Neural retina-specific leucine zipper protein (NRL)

6.6

Glial cell line-derived neurotrophic factor (GDNF)

3.4

Heregulin-beta2; glial growth factor; neuregulin

2.1

Brain-derived neurotrophic factor (BDNF)

1.7

Glia-derived neurite-promoting factor (GDNPF)

1.6

Neurotrophic tyrosine kinase receptor-related 3

1.5

Up-regulated in PBC compared to PSC

 

Synapse associated protein 97 (SAP97); homolog of Drosophila discs large isoform 1 (HDLG1)

2.3

 

Table 9 The Twenty Most Down-Regulated genes in PBC

Compared to Non-diseased Liver

Down-regulation in PBC Compared to Non-Diseased Liver

Ratio

Ephrin A3 (EFNA3)

-13.0

CC chemokine receptor type 2 (CC CKR2; CCR2); monocyte chemoattractant protein 1 receptor (MCP1R)

-11.4

Interferon-alpha2 (IFN-alpha; IFNA)

-9.9

Interleukin-12 receptor (IL-12R)

-7.5

TNF-related apoptosis inducing ligand (TRAIL); APO-2 ligand (APO2L)

-7

Interferon gamma antagonist (IFN-gamma antagonist)

-6.4

Stem cell factor (SCF, c-kit ligand)

-6

Cytotoxic ligand TRAIL receptor

-5.7

Ephrin B3

-5.7

G2/mitotic-specific cyclin B1 (CCNB1)

-5.6

Migration inhibitory factor-related protein 14 (MRP-14); calgranulin B

-5.5

Interleukin-1 receptor type II (IL-1R2); IL-1R-beta

-4.2

Migration inhibitory factor-related protein 8 (MRP-8); calgranulin A

-4.2

High-affinity interleukin-8 receptor A (IL-8R A); IL-8 receptor type 1; CD128

-3.9

Neural-cadherin (N-cadherin; NCAD)

-3.9

G1/S-specific cyclin E (CCNE)

-3.9

Bone morphogenetic protein 2A (BMP2A)

-3.8

Bone morphogenetic protein 3 (BMP3); osteogenin

-3.7

Interleukin 10 receptor (IL-10R)

-3.7

insulin-like growth factor II (IGF II)

-3.5

Table 9

(A) The forty most up-regulated genes in PBC compared to non-diseased liver tissue

(B) The forty most up-regulated genes in PBC compared to PSC liver tissue

(A) Up-regulated in PBC Compared to Non-Diseased Liver tissue

Ratio

Brain-derived neurotrophic factor (BDNF) receptor (Trk3)

29.4

Connective tissue growth factor (CTGF)

13.6

Transforming growth factor-beta 3 (TGF-beta3)

12.6

Wnt-2; int-1 related protein (IRP)

12.6

Synapse-associated protein 97 (SAP97); homolog of Drosophila discs large protein isoform 1 (HDLG1)

12.5

Follistatin

10.7

Stem cell protein (SCL, TAL-1)

9.0

Jagged-1 (HJ1)

7.9

Transcription factor LSF

7.4

Stromal cell derived factor 1 receptor (SDF-1 receptor; CXCR4)

7.2

Papillary thyroid carcinoma-encoded protein + ret proto-oncogene

7.1

Tyrosine-protein kinase receptor flt3; CD135

6.8

Patched homolog (PTC)

6.7

Neural retina-specific leucine zipper protein (NRL)

6.6

DNA damage repair & recombination protein 52 (Rad52)

6.1

Follicle stimulating hormone receptor (FSHR); follitropin receptor

6.0

Prohibitin (PHB)

6.0

Proto-oncogene c-jun; transcription factor AP-1

5.9

Wnt-13

5.7

Myeloid cell nuclear differentiation antigen (MNDA)

5.7

Prorelaxin H2 (RLN2)

5.5

Delta-like protein (DLK)

5.3

Neurogenic locus notch protein (N)

5.2

Platelet-activating factor receptor (PAFR)

5.0

Ataxia telangiectasia (ATM)

4.9

Neurogenic locus notch protein homolog 1 (Notch-1)

4.7

C-src proto-oncogene (SRC1)

4.5

Thrombomodulin (THBD; THRM)

4.5

Frizzled-related FrzB (FRITZ) + FrzB + frezzled (FRE)

4.4

Growth arrest & DNA-damage-inducible protein (GADD45)

4.3

DNA-dependent protein kinase (DNA-PK) + DNA-PK catalytic subunit (DNA-PKCS)

4.3

Nuclear respiratory factor 1 (NRF1)

4.2

Early response protein NAK1; TR3 orphan receptor

4.1

Transcription initiation factor 250-kDa subunit (TAFII250)

4.0

Muscle-specific DNase I-like

4.0

Interleukin-17 (IL-17)

4.0

Glutathione S-transferase M1

4.0

DNA ligase IV (LIG4)

3.7

Interleukin-5 (IL-5)

3.6

70-kDa heat shock protein 1 (HSP70.1; HSPA1)

3.6

(B) Up-regulated in PBC compared to PSC Liver Tissue

Transcription initiation factor 250-kDa subunit (TAFII250)

85.5

Papillary thyroid carcinoma-encoded protein + ret proto-oncogene

19.3

Wnt-13

8.7

interleukin-3 (IL-3)

7.8

Interleukin-15 (IL-15)

6.5

Wnt-5a

6.3

Patched homolog (PTC)

4.1

Notch-2

4.0

Prorelaxin H2 (RLN2)

3.8

Renin-binding protein (RENBP; RNBP)

3.7

Follicle stimulating hormone receptor (FSHR)

3.6

Notch-4; hnotch-4

3.4

Angiotensin II type 1A receptor (AT1AR)

3.4

Interleukin-17 (IL-17)

3.2

Paired box homeotic protein (PAX8) isoforms 8A/8B + isoforms 8C/8D

3.1

CCAAT-binding transcription factor subunit B (CBF-B)

3.0

Ataxia telangiectasia (ATM)

3.0

Neurogenic locus notch protein homolog 1 (Notch-1)

3.0

Follistatin

3.0

Jagged-1 (HJ1)

2.9

DNA ligase IV (LIG4)

2.9

Wnt-10b; Wnt-12

2.8

Thrombomodulin (THBD)

2.8

Neurogenic locus notch protein (Notch)

2.8

Transforming growth factor-beta 3 (TGF-beta3)

2.7

Growth arrest & DNA-damage-inducible protein 153 (GADD153)

2.7

Erb B4 receptor protein-tyrosine kinase; Her4 tyrosine kinase-EGF receptor related

2.7

Heat shock 27-kDa protein (HSP27)

2.6

Jagged-2 (JAG2)

2.6

DNA damage repair & recombination protein 52 (Rad52)

2.6

DNA-dependent protein kinase (DNA-PK) + DNA-PK catalytic subunit (DNA-PKCS)

2.6

Interleukin-5 (IL-5)

2.6

Kidney epidermal growth factor (EGF)

2.5

Smoothened; GX

2.5

Thrombin receptor (TR)

2.5

Connective tissue growth factor (CTGF)

2.5

Frizzled-related FrzB (FRITZ) + FrzB + frezzled (FRE)

2.4

Met proto-oncogene; hepatocyte growth factor receptor (HGF-SF receptor)

2.4

Early response protein NAK1 TR3 orphan receptor

2.4

Basic transcription element-binding protein 2 (BTEB2); GC-box binding protein 2

2.4