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

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.

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-regulated in PSC Compared to Non-Diseased Liver

Ratio

Interleukin-8 (IL-8)

9.9

Granulocyte colony-stimulating factor (G-CSF)

9.1

T-cell-secreted protein I-309 ; small inducible cytokine A1 (SCYA1)

8.1

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

7.1

Interleukin-3 (IL-3)

6.3

Interleukin-11 (IL-11)

5.8

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

4.9

Stromal cell derived factor 1 receptor (SDF1 receptor; CXCR4)

4.8

Interferon-alpha/beta receptor alpha subunit (IFN-alpha receptor; IFNAR)

4.3

Endothelial-monocyte activating polypeptide II (EMAP II)

4.3

Interleukin-13 (IL-13)

4.2

Macrophage inflammatory protein 1 alpha receptor (MIP1alpha R); RANTES R; CCR5

4.0

Interleukin-6 receptor alpha subunit (IL-6R-alpha; IL6R)

3.9

Cytokine receptor EBI3

3.9

Interferon-gamma induced protein (gamma-IP10)

3.8

PAI3; plasminogen activator inhibitor 3 (PLANH3)

3.7

Interferon-alpha2 (IFN-alpha)

3.7

Tyrosine-protein kinase receptor flt3; CD-135

3.7

E-selectin ; endothelial leukocyte adhesion molecule 1 (ELAM-1)

3.5

Integrin beta 1; VLA4 beta; CD29

3.4

Interleukin-12 beta subunit (IL-12B)

3.4

Interleukin-14 (IL-14)

3.3

Interferon-beta (IFN-beta; IFNB)

3.1

Interferon gamma (IFN-gamma; IFNG)

2.9

Macrophage migration inhibitory factor (MIF)

2.8

Interferon-alpha/beta receptor beta subunit (IFN-alpha-R)

2.7

Interleukin-2 receptor (CD25) gamma subunit (IL-2R gamma; IL2RG)

2.6

CD40 receptor-associated factor 1 (CRAF1)

2.6

Interleukin-12 alpha subunit (IL-12A)

2.5

Phospholipase A2 (PLA2)

2.3

Interferon-gamma (IFN-gamma) receptor beta subunit

2.3

Macrophage inflammatory protein 1 beta (MIP1-beta)

2.2

Interleukin-1 beta (IL-1 ; IL1B)

2.2

Integrin alpha 6; VLA6; CD49f antigen

2.2

CD40 ligand (CD40-L)

2.2

Integrin beta 6

2.1

Monocyte chemotactic protein 1 (MCP1)

2.1

Interleukin-2 receptor (CD25) beta subunit (IL-2 receptor beta; IL2RB)

2.1

C5a anaphylatoxin receptor (C5AR)

2.0

Integrin alpha 5; VLA5; CD49e

2.0

Lymphotoxin-beta (LT-beta; LTB)

2.0

Stromal cell derived factor 1 alpha; Fusin; SDF1A; CXC4

1.9

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

1.9

Interferon-gamma receptor (IFNR-gamma; IFNGR1); CDw119 antigen

1.8

Interleukin-5 receptor alpha subunit (IL-5R-alpha; IL5RA)

1.8

CD4; T-cell surface glycoprotein T4

1.7

HLA class I histocompatibility antigen C-4 alpha subunit

1.7

Leukosialin; CD43

1.7

Tumor necrosis factor receptor (TNFR)

1.6

Integrin alpha 2B

1.6

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

1.6

Semaphorin; CD100

1.5

Interferon consensus sequence-binding protein (ICSBP)

1.5

Tumor necrosis factor (TNF-alpha)

1.5

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

1.5

Up-regulated in PSC compared to PBC

 

Interferon-alpha/beta receptor beta subunit (IFN-alpha-R)

19.7

T-cell-secreted protein I-309 ; small inducible cytokine A1(SCYA1)

14.3

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

12.2

Interferon-alpha2 (IFN-alpha; IFNA)

9.8

Granulocyte colony-stimulating factor (G-CSF)

9.8

Integrin beta 6

8.6

Interleukin-3 (IL-3)

8.0

Interferon-alpha/beta receptor alpha subunit (IFN-alpha receptor; IFNAR)

7.0

Interleukin-11 (IL-11)

7.0

Interferon gamma (IFN-gamma; IFNG)

5.5

Endothelial-monocyte activating polypeptide II (EMAP II)

5.3

Interleukin-11 (IL-11)

4.8

Interleukin-8 (IL-8)

4.7

Interleukin-12 alpha subunit (IL-12A)

4.7

Cytokine receptor EBI3

4.6

Interleukin-14 (IL-14)

4.5

Interleukin-1 beta (IL-1 ; IL1B); catabolin

4.2

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

3.8

Interleukin-13 (IL-13)

3.7

Interleukin-5 receptor alpha subunit (IL-5R-alpha; IL5RA)

3.7

Interleukin-6 receptor alpha subunit (IL-6R-alpha; IL6R)

3.2

Interferon-gamma induced protein (gamma-IP10)

3.0

CD40 receptor-associated factor 1 (CRAF1)

3.0

Macrophage inflammatory protein 1 beta (MIP1-beta)

2.8

Interferon-gamma receptor (IFNR-gamma; IFNGR1)

2.4

Phospholipase A2 (PLA2)

2.3

Integrin beta 1; VLA4 beta; CD29

2.2

Integrin alpha 2B

2.2

Interleukin-12 beta subunit (IL-12B)

2.2

Macrophage inflammatory protein 1 beta (MIP1-beta)

2.1

Macrophage migration inhibitory factor (MIF)

1.9

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

1.7

Interleukin-2 receptor beta subunit (IL-2 receptor beta; IL2RB)

1.7

Interferon-gamma (IFN-gamma) receptor beta subunit

1.6

Macrophage inflammatory protein 1 alpha receptor (MIP1alpha R); RANTES R; CCR5

1.5

Integrin alpha 5; VLA5; CD49e

1.5

 

 

Table 2 Fibrosis Associated Genes

Up-regulated in PSC Compared to Non-Diseased Liver

Ratio

Connective tissue grwoth factor (CTGF)

4.2

Platelet-activating factor receptor (PAFR)

2.8

Platelet-derived growth factor receptor beta subunit (PDGFRB)

2.6

Platelet-derived growth factor A subunit (PDGFA; PDGF-1)

2.1

N-sam; fibroblast growth factor receptor1 (FGFR1); basic fibroblast growth factor receptor (bFGFR)

2.1

Cysteine-rich fibroblast growth factor receptor

1.9

Fibroblast growth factor 8 (FGF8)

1.7

Fibroblast growth factor 12; FHF-1

1.6

Platelet-derived growth factor (PDGF) associated protein

1.6

Up-regulated in PSC compared to PBC

 

Platelet-derived growth factor A subunit (PDGFA; PDGF-1)

2.6

Platelet-derived growth factor (PDGF) associated protein

2.0

Fibroblast growth factor 8 (FGF8)

1.5

 

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

Up-regulated in PSC Compared to Non-Diseased Liver

Ratio

Brain-derived neurotrophic factor (BDNF)

38.6

Protein serine/threonine kinase STK1; cell division protein kinase 7 (CDK7)

9.2

Thrombopoietin receptor (TPOR)

9.0

Insulin-like growth factor IA (IGF1A)

7.6

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

6.8

Amphiregulin (AR); colorectum cell-derived growth factor (CRDGF)

5.0

Transferrin receptor; CD71

4.9

Insulin-like growth factor binding protein 2 (IGFBP2)

4.2

Insulin-like growth factor II receptor (IGFR II)

3.7

G2/mitotic-specific cyclin B1 (CCNB1)

3.6

T-lymphocyte maturation-associated protein MAL

3.4

G1/S-specific cyclin D3 (CCND3)

3.3

Erb B2 receptor protein-tyrosine kinase; neu proto-oncogene; c-erb B2 + HER2 receptor

3.0

Insulin-like growth factor-binding protein 3 (IGFBP3)

3.0

Insulin-like growth factor binding protein 5 (IGFBP5)

2.9

Insulin-like growth factor binding protein 1 (IGFBP1)

2.9

Glial cell line-derived neurotropic factor (GDNF)

2.9

Cyclin-dependent kinase inhibitor 3 (CDKN3)

2.8

Vascular endothelial growth factor C (VEGF-C); FLT4 ligand

2.6

Beta nerve growth factor (NGF)

2.4

Insulin-like growth factor II (IGF2)

2.4

Heregulin-beta3; glial growth factor; neuregulin

2.3

Thrombopioten (THPO)

2.3

Growth factor receptor-bound protein 2 (GRB2) isoform

2.3

Glia-derived neurite-promoting factor (GDNPF)

2.1

Beta Ig-H3 (BIGH3); Kerato-Epithelin

2.0

Insulin-like growth factor binding protein 6 (IGFBP6)

2.0

Insulin-like growth factor binding protein 2 (IGFBP2)

1.9

Insulin receptor (INSR)

1.8

Epidermal growth factor receptor substrate 15 (EPS15)

1.8

G1/S-specific cyclin D2 (CCND2)

1.7

Neurogenic locus notch protein homolog 1 (NOTCH1)

1.6

Epidermal growth factor receptor (EGFR)

1.6

Neuromodulin (GAP-43)

1.5

Adenomatous polyposis coli protein (APC protein)

1.5

G1/S-specific cyclin D1 (CCND1)

1.5

Tyrosine-protein kinase receptor UFO (axl)

1.5

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

1.5

High-affinity nerve growth factor receptor

1.5

Up-regulated in PSC compared to PBC

 

Thrombopoietin receptor (TPOR)

19.7

Insulin-like growth factor IA (IGF1A)

9.6

Amphiregulin (AR); colorectum cell-derived growth factor (CRDGF)

7.7

G2/mitotic-specific cyclin B1 (CCNB1)

5.4

Protein serine/threonine kinase STK1; cell division protein kinase 7 (CDK7)

4.6

Transferrin receptor; CD71

3.7

Brain-derived neurotrophic factor (BDNF)

3.4

Beta nerve growth factor (NGF)

2.9

Insulin-like growth factor binding protein 1 (IGFBP1)

2.4

Growth factor receptor-bound protein 2 (GRB2) isoform

2.2

Insulin-like growth factor II receptor (IGFR II)

2.1

Insulin-like growth factor binding protein 2 (IGFBP2)

2.0

Insulin-like growth factor binding protein 5 (IGFBP5)

1.9

Insulin-like growth factor II (IGFII)

1.9

T-lymphocyte maturation-associated protein MAL

1.7

Neuro epithelioma transforming gene 1 (NEP1; NET1)

1.7

High-affinity nerve growth factor receptor

1.7

Insulin-like growth factor-binding protein 3 (IGFBP3)

1.6

Neuromodulin (GAP-43)

1.5

Table 4 Intracellular Signalling and Nuclear Associated Genes

 

Up-regulated in PSC Compared to Non-Diseased Liver

Ratio

Serine/threonine-protein kinase NRK2; Serine threonine kinase 2 (STK2)

12.8

Stem cell protein (SCL, TAL-1)

7.0

Protein-tyrosine phosphatase gamma (R-PTP-gamma)

7.0

Calcium/calmodulin-dependent protein kinase type IV catalytic subunit (CAMK IV)

6.3

cAMP response element binding protein (CRE-BP1)

5.7

c-Fer proto-oncogene

5.6

n-Myc proto-oncogene

5.4

Dihydropyridine-sensitive L-type calcium channel beta-3 subunit (CAB3A/CAB3B)

4.8

Ras related protein Rab5A

4.4

SnoN oncogene

4.1

Ras related protein Rab3B

4.0

MutL protein homolog; DNA mismatch repair protein MLH1

3.8

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

3.7

Proto-oncogene tyrosine-protein kinase lck; p56-lck

3.6

Transcription factor ZFM1

3.4

Neurotrophic tyrosine kinase receptor-related 3

3.2

DNA-binding protein inhibitor ID-1; Id-1H

3.2

Guanine nucleotide regulatory protein alpha-13 subunit

3.1

Retinoic acid receptor beta (RXR-beta; RXRB)

3.0

p53 cellular tumor antigen

2.9

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

2.7

Colon carcinoma kinase 4 (CCK4)

2.6

Mdm2 protein; p53-associated protein + mdm2-A + mdm2-C

2.6

Integrin-linked kinase (ILK)

2.5

CACCC-box DNA-binding protein

2.5

Dual-specificity mitogen-activated protein kinase kinase 6 (MAP kinase kinase 6

2.4

Janus kinase 1 (JAK1)

2.4

Cytoplasmic antiproteinase 3 (CAP3)

2.4

MacMARCKS; MARCKS-related protein

2.3

Prostaglandin E2 (PGE) receptor EP4 subtype

2.3

NF-kappaB transcription factor p65 subunit

2.2

Jun-D

2.2

Guanine nucleotide regulatory protein tim1

2.2

Tyrosine kinase tnk1

2.1

RNA polymerase II elongation factor SIII p15 subunit

2.1

ras-related protein Rab4A

2.1

Neural-cadherin (N-cadherin; NCAD); cadherin 2 (CDH2)

2.1

c-Jun N-terminal kinase 3 alpha2 (JNK3A2)

2.0

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

2.0

DNA-repair protein XRCC1

2.0

Transducer of Erb B2 (TOB)

2.0

Tyk2 non-receptor protein tyrosine kinase

2.0

MAPKAP kinase (3pK)

2.0

Transforming protein rhoA H12 (RHO12; ARH12; ARHA)

2.0

Plasma membrane calcium-transporting ATPase isoform 2 (PMCA2)

1.9

Fos-related antigen 1 (FRA1)

1.9

Neurogenic locus notch protein (N)

1.9

Helix-loop-helix protein HLH 1R21

1.8

3�5�-cAMP phosphodiesterase HPDE4A6

1.8

Signal transducer and activator of transcription 6 (STAT6); IL-4 STAT

1.8

GTP-binding protein ras associated with diabetes (Rad1)

1.8

Guanine nucleotide-binding protein G-s alpha subunit

1.8

DNA polymerase alpha catalytic subunit (POLA)

1.7

Activin type I receptor

1.7

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

1.7

V-erbA related protein (EAR3)

1.7

FUSE binding protein

1.6

Ini1

1.6

cAMP-dependent protein kinase type I beta regulatory subunit (PRKAR1B)

1.6

c-Jun N-terminal kinase kinase 1 (JNKK)

1.6

Transcription factor TFIIB

1.6

Xeroderma pigmentosum group G complementing protein (XPG)

1.5

Xeroderma pigmentosum group B complementing protein (XPB)

1.5

c-myc oncogene

1.5

DNA excision repair protein ERCC1

1.5

Mitogen-activated protein kinase p38 (MAP kinase p38)

1.5

DNA-binding protein HIP116

1.5

c-jun N-terminal kinase 2 (JNK2)

1.5

Up-regulated in PSC compared to PBC

 

Neural-cadherin (N-cadherin; NCAD)

6.1

Serine/threonine-protein kinase NRK2; Serine threonine kinase 2 (STK2)

4.5

Cytoplasmic antiproteinase 3 (CAP3)

4.3

Ras related protein Rab5A

4.2

Ras related protein Rab3B

3.8

Dihydropyridine-sensitive L-type calcium channel beta-3 subunit (CAB3A/CAB3B)

3.0

Proto-oncogene tyrosine-protein kinase lck; p56-lck

2.9

SnoN oncogene

2.7

Retinoic acid receptor beta (RXR-beta; RXRB)

2.7

14-3-3n protein eta; protein AS1

2.6

n-Myc proto-oncogene

2.6

CAMP response element binding protein (CRE-BP1); transcription factor ATF2; HB16

2.6

Protein-tyrosine phosphatase gamma (R-PTP-gamma)

2.5

Mdm2 protein; p53-associated protein + mdm2-A + mdm2-C

2.4

Dual-specificity mitogen-activated protein kinase kinase 6 (MAP kinase kinase 6

2.4

Tyk2 non-receptor protein tyrosine kinase

2.4

Calcium/calmodulin-dependent protein kinase type IV catalytic subunit (CAMK IV)

2.3

Guanine nucleotide regulatory protein alpha-13 subunit

2.3

Phospholipase C (PLCL)

1.9

Ras-related protein Rab4A

1.9

Plasma membrane calcium-transporting ATPase isoform 2 (PMCA2)

1.9

3�5�-cAMP phosphodiesterase HPDE4A6

1.9

Integrin-linked kinase (ILK)

1.8

FUSE binding protein

1.8

Janus kinase 1 (JAK1)

1.7

Ini1

1.6

MacMARCKS; MARCKS-related protein (MRP)

1.5

Prostaglandin E2 (PGE) receptor EP4 subtype (PTGER4; PTGER2)

1.5

Tyrosine-protein kinase lyn

1.5

RNA polymerase II elongation factor SIII p15 subunit

1.5

MAPKAP kinase (3pK)

1.5

 

Table 5 Apoptosis Associated Genes

Up-regulated in PSC Compared to Non-Diseased Liver

Ratio

Caspase-2 (CASP2)

4.3

Inhibitor of apoptosis protein 2 (IAP2)

4.2

Bcl-2 homologous antagonist/killer (BAK)

3.9

Caspase-6 (CASP6)

3.9

Bcl-2

3.7

Inhibitor of apoptosis protein1 (IAP1)

3.6

Bcl-2-related protein A1 (Bcl-2A1; BFL1)

3.3

Bcl-2 Adenovirus E1B 19kD Interacting Protein (NIP1)

3.2

Bcl-2 interacting killer (BIK)

2.9

Receptor interacting protein; cell death protein RIP

2.6

Inhibitor of apoptosis protein 3 (IAP3)

2.6

Bcl-x

2.6

Apoptosis regulator bax

2.5

WSL protein + TRAMP + Apo-3 + death domain receptor 3 (DDR3)

2.5

Caspase-8 (CASP8)

2.2

Early response protein NAK1; TR3 orphan receptor

2.2

Cysteine protease ICE-LAP3

2.2

Caspase-4 (CASP4)

1.9

Secreted apoptosis related protein 1 (SARP1)

1.8

Caspase-10 (CASP10)

1.7

Caspase-3 (CASP-3)

1.7

Up-regulated in PSC compared to PBC

 

Bcl-2-related protein A1 (Bcl-2A1 BFL1)

5.7

Inhibitor of apoptosis protein1 (I AP1)

5.1

Inhibitor of apoptosis protein 2 (IAP2)

4.9

Caspase-6 (CASP6)

4.3

Receptor interacting protein; cell death protein RIP

2.9

Cysteine protease ICE-LAP3

2.9

Bcl-x

2.8

Caspase-2 (CASP2)

2.7

Bcl-2 Adenovirus E1B 19kD Interacting Protein (NIP1)

2.7

Bcl-2

2.3

Bcl-2 interacting killer (BIK)

2.2

Inhibitor of apoptosis protein 3 (IAP3)

2.2

WSL protein + TRAMP + Apo-3 + death domain receptor 3 (DDR3)

2.2

Apoptosis regulator bax

1.6

Caspase-8 (CASP8)

1.5

 

Table 6 Stress Response Associated Genes

 

Up-regulated in PSC Compared to Non-Diseased Liver

Ratio

Cytosolic superoxide dismutase 1 (SOD1)

3.5

Glutathione S-transferase M1

2.9

Ionizing Radiation resistance-conferring protein + death-associated protein 3 (DAP3)

2.8

Dioxin-inducible cytochrome P450 1B1 (CYP1B1)

2.7

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

2.7

Glutaredoxin

2.7

Inducible nitric oxide synthase (iNOS)

2.6

Heat shock 90-kDa protein A (HSP90A)

2.6

Heat shock factor protein 1 (HSF1)

2.2

Heat shock protein 60 (HSP-60)

1.9

Glutathione reductase (GSR)

1.8

Glutathione peroxidase (GSHPX1)

1.7

Heat shock 27-kDa protein (HSP27)

1.5

Cytoplasmic dynein light chain 1 (HDLC1); protein inihibitor of neuronal nitric oxide synthase (PIN)

1.5

Liver glutathione S-transferase subunit 1

1.5

Up-regulated in PSC compared to PBC

 

Ionizing Radiation resistance-conferring protein + death-associated protein 3 (DAP3)

3.8

Glutaredoxin

2.0

Cytosolic superoxide dismutase 1 (SOD1)

1.6

 

Table 7 Uncategorised Genes

 

Up-regulated in PSC Compared to Non-Diseased Liver

Ratio

Bullous pemphigoid antigen 1 (BPAG1; BPA)

6.1

Retinoic acid receptor epsilon (RAR-epsilon)

5.8

Adenosine A3 receptor (ADORA3)

4.8

60S ribosomal protein L6 (RPL6)

4.8

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

4.7

40S ribosomal protein S9

4.2

Cellular retinoic acid-binding protein II (CRABP2)

4.1

Preprotachykinin beta (beta-PPT); substance K

4.1

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

3.6

Follistatin-related protein

3.6

Ephrin type-B receptor 2 precursor

3.3

14-3-3n protein eta; protein AS1; YWHAH; YWHA1

3.3

Brain-specific tubulin alpha 1 subunit (TUBA1)

3.3

Mitochondrial matrix protein P1

3.2

cAMP-response element binding protein (CREB)

3.2

Adenosine A2A receptor (ADORA2A)

3.1

Ubiquitin-conjugating enzyme E2 17-kDa (UBE2A)

3.0

Orphan hormone nuclear receptor

2.8

Urokinase-type plasminogen activator receptor GPI-anchored form (U-PAR)

2.8

FAN protein

2.8

Neuro epithelioma transforming gene 1 (NEP1; NET1)

2.5

Tumor suppressor LUCA1; hyaluronoglucosaminidase (HYAL1)

2.5

Activator 1 37-kDa subunit

2.5

23-kDa highly basic protein

2.4

LIM domain kinase 1 (LIMK-1)

2.4

40S ribosomal protein S19 (RPS19)

2.4

Neurotrophin-4 (NT-4)

2.3

Protein-tyrosine phosphatase zeta (R-PTP-zeta)

2.3

Protein-tyrosine phosphatase 1E

2.3

Ephrin type-B receptor 4

2.2

Ephrin B2

2.2

Replication protein A 70-kDa subunit (RPA70; REPA1; RF-A); single-stranded DNA-binding protein

2.2

Tyrosine kinase lyn

2.1

Neurotrophin-4 (NT4); NT5 + NT6-alpha + NT6-beta + NT6-gamma

2.1

Ribonuclease/angiogenin inhibitor (RAI)

2.1

40S ribosomal protein S9

1.9

Protein kinase C beta I

1.9

Heparin-binding growth factor 8 (HBGF-8)

1.9

Thymosin beta-10

1.9

Autocrine motility factor receptor (AMF receptor; AMFR)

1.8

Cytoplasmic beta-actin (ACTB)

1.8

Ephrin type-A receptor 1

1.8

Ephrin B3

1.7

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

1.7

Prothymosin alpha

1.7

Liver glyceraldehyde 3-phosphate dehydrogenase (GAPDH)

1.6

Angiotensin-converting enzyme (ACE)

1.5

Neuromedin B receptor (NMBR)

1.5

Ubiquitin

1.5

Up-regulated in PSC compared to PBC

 

Retinoic acid receptor epsilon (RAR-epsilon)

5.5

Bullous pemphigoid antigen 1 (BPAG1; BPA)

4.6

Adenosine A3 receptor (ADORA3)

3.9

Adenosine A1 receptor (ADORA1)

3.9

Adenosine A2A receptor (ADORA2A)

3.9

23-kDa highly basic protein

3.7

Ephrin-B2

3.6

Neurotrophin-4 (NT-4)

3.6

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

3.6

Ephrin-B3

3.1

Protein-tyrosine phosphatase zeta (R-PTP-zeta)

3.0

40S ribosomal protein S9

2.7

Preprotachykinin beta (beta-PPT); substance K

2.7

40S ribosomal protein S19 (RPS19)

2.5

P53 cellular tumor antigen

2.4

FAN protein

2.3

Urokinase-type plasminogen activator receptor GPI-anchored form (U-PAR)

2.1

Neuromedin B receptor (NMBR)

1.9

Ubiquitin-conjugating enzyme E2 17-kDa (UBE2A)

1.7

Tumor suppressor LUCA1

1.7

Protein-tyrosine phosphatase 1E

1.7

Ribonuclease/angiogenin inhibitor (RAI)

1.6

Table 8 Neural Associated Genes

Up-regulated in PSC Compared to Non-Diseased Liver

Ratio

Brain-derived neurotrophic factor (BDNF)

38.6

Preprotachykinin beta (beta-PPT); substance K

4.1

Beta nerve growth factor (NGF)

2.4

Neurotrophin-4 (NT-4)

2.3

Glia-derived neurite-promoting factor (GDNPF)

2.1

Neuromodulin (GAP-43)

1.5

Up-regulated in PSC compared to PBC

 

Neurotrophin-4 (NT-4)

3.6

Brain dreived neurotrophic factor (BDNF)

3.4

Beta-nerve growth factor (NGF)

2.9

Preprotachykinin beta (beta-PPT); substance K

2.7

Neuromedin B receptor (NMBR)

1.9

Neuro epithelioma transforming gene 1 (NEP1;NET1)

1.7

High affinity nerve growth factor receptor

1.7

Neuromodulin (GAP-43)

1.5

 

Table 9 The Twenty Most Down-Regulated genes in PSC Compared to Non-diseased Liver

Down-regulation in PSC Compared to Non-Diseased Liver

Ratio

Ephrin A3 (EFNA3)

-6.2

Vascular endothelial growth factor C (VEGF-C); FLT4 ligand

-5.4

Insulin-like growth factor II (IGF2); somatomedin A

-5.2

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

-4.8

Macrophage inflammatory protein 2 alpha (MIP2-alpha); growth-regulated protein beta (GRO-beta)

-4

Oncostatin M (OSM)

-3.6

Notch2

-3.5

Epithelial discoidin domain receptor 1 (EDDR1)

-3.5

Acyl-CoA-binding protein (ACBP); diazepam binding inhibitor (DBI); endozepine (EP)

-3.5

c-Myc purine-binding transcription factor puf

-3.4

Interleukin-1 receptor antagonist protein (IL-1RA; IRAP)

-3.4

Dual-specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1; MAPKK 1; MKK1)

-3.4

Bone morphogenetic protein 2A (BMP2A)

-3.3

Microsomal glutathione S-transferase 12 (GST12; MGST1)

-3.2

DNA-binding protein SMBP-2; glial factor-1 (GF-1)

-3.1

SL cytokine ; FLT3 ligand (FLT3LG)

-3.1

Cytotoxic ligand TRAIL receptor

-3.1

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

-2.9

Interleukin-12 receptor (IL-12R)

-2.9

Mitochondrial transcription factor 1 (MTTF1); TCF6L1

-2.8

Table 10 (A) The forty most upregulated genes in PSC compared to non-diseased liver

(B) The forty most upregulated genes in PSC compared to PBC liver

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

Ratio

Brain-derived neurotrophic factor (BDNF)

38.6

Serine/threonine-protein kinase NRK2; serine/threonine kinase 2 (STK2)

12.8

Interleukin-8 (IL-8)

9.9

Protein serine/threonine kinase STK1; cell division protein kinase 7 (CDK7)

9.2

Granulocyte colony-stimulating factor (G-CSF)

9.1

Thrombopoietin receptor (TPOR)

9.0

T-cell-secreted protein I-309 ; small inducible cytokine A1 (SCYA1)

8.1

Insulin-like growth factor IA (IGF1A)

7.6

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

7.1

Protein-tyrosine phosphatase gamma (R-PTP-gamma)

7.0

Stem cell protein (SCL, TAL-1)

7.0

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

6.8

Calcium/calmodulin-dependent protein kinase type IV catalytic subunit (CAMK IV)

6.3

Interleukin-3 (IL-3)

6.3

Bullous pemphigoid antigen 1 (BPAG1; BPA)

6.1

Retinoic acid receptor epsilon (RAR-epsilon); HAP

5.8

Interleukin-11 (IL-11)

5.8

cAMP response element binding protein (CRE-BP1)

5.7

C-fer proto-oncogene

5.6

N-myc proto-oncogene

5.4

Amphiregulin (AR); colorectum cell-derived growth factor (CRDGF)

5.0

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

4.9

Transferrin receptor; CD71

4.9

Dihydropyridine-sensitive L-type calcium channel beta-3 subunit (CAB3A/CAB3B)

4.8

Stromal cell derived factor 1 receptor (SDF1 receptor; CXCR4)

4.8

60S ribosomal protein L6 (RPL6)

4.8

Adenosine A3 receptor (ADORA3)

4.8

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

4.7

Ras-related protein Rab5A

4.4

Interferon-alpha/beta receptor alpha subunit

4.3

Caspase-2 (CASP2)

4.3

Endothelial-monocyte activating polypeptide II (EMAP II)

4.3

Connective tissue growth factor (CTGF)

4.2

Insulin-like growth factor binding protein 2 (IGFBP2)

4.2

Interleukin-13 (IL-13)

4.2

Inhibitor of apoptosis protein 2 (IAP2)

4.2

40S ribosomal protein S9

4.2

Cellular retinoic acid-binding protein II (CRABP2)

4.1

SnoN oncogene

4.1

(B) Up-regulated in PSC compared to PBC

Thrombopoietin receptor (TPOR)

19.7

Interferon-alpha/beta receptor beta subunit (IFN-alpha-R)

19.7

T-cell-secreted protein I-309 ; small inducible cytokine A1 (SCYA1)

14.3

Migration inhibitory factor-related protein 14 (MRP-14)

12.2

Interferon-alpha2 (IFN-alpha; IFNA)

9.8

Granulocyte colony-stimulating factor (G-CSF)

9.8

Insulin-like growth factor IA (IGF1A)

9.6

Integrin beta 6 (ITGB6)

8.6

Interleukin-3 (IL-3)

8.0

Amphiregulin (AR); colorectum cell-derived growth factor (CRDGF)

7.7

Interferon-alpha/beta receptor alpha subunit (IFN-alpha receptor; IFNAR)

7.0

Interleukin-11 (IL-11)

7.0

Neural-cadherin (N-cadherin; NCAD)

6.1

BCL-2-related protein A1 (BCL2A1 BFL1)

5.7

Retinoic acid receptor epsilon (RAR-epsilon)

5.5

Interferon gamma (IFN-gamma; IFNG)

5.5

G2/mitotic-specific cyclin B1 (CCNB1)

5.4

Endothelial-monocyte activating polypeptide II (EMAP II)

5.3

Inhibitor of apoptosis protein1 (IAPI1)

5.1

Inhibitor of apoptosis protein 2 (IAP2)

4.9

Interleukin-12 alpha subunit (IL-12A)

4.7

Interleukin-8 (IL-8)

4.7

Protein serine/threonine kinase STK1; cell division protein kinase 7 (CDK7)

4.6

Cytokine receptor EBI3

4.6

Bullous pemphigoid antigen 1 (BPAG1; BPA)

4.6

Interleukin-14 (IL-14)

4.5

Serine/threonine-protein kinase NRK2

4.5

Caspase-6 (CASP6)

4.3

Cytoplasmic antiproteinase 3 (CAP3)

4.3

Interleukin-1 beta (IL-1 ; IL1B)

4.2

Ras-related protein Rab5A

4.2

Adenosine A2A receptor (ADORA2A)

3.9

Adenosine A1 receptor (ADORA1)

3.9

Adenosine A3 receptor (ADORA3)

3.9

Ionizing Radiation resistance-conferring protein + death-associated protein 3 (DAP3)

3.8

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

3.8

Ras-related protein Rab3B

3.8

Interleukin-13 (IL-13)

3.7