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. 2015 Mar 31;112(7):1141–1156. doi: 10.1038/bjc.2015.38

Table 8. Summary of proteomic studies that were reviewed.

Protein (key role) UniProt ID Biofluid Relation to HCC (↑, ↓) HCC LB rate Cohort sizes Aetiology AUROC Fold change Platform Reference
AGP1 (AP: Transport) P02763 Plasma ↑ HCC:CON No information *10 HCC; 30 controls (healthy/LC/HBV) HBV 0.73 1.6* Lectin MRM–UPLC–ESI–MS Ahn et al, 2012a, 2012b*
    Plasma ↓ HCC:LC No information Disc: 10 HCC/2 HCON Val: 18 HCC, 10 HCON No information 0.65 nUPLC–ESI–QTOF–MS and QQQ Lee et al, 2011
    Serum ↑ HCC:LC 100% ALL Disc: 9 HCC/9 LC Val: 52 HCC/40 LC HBV 1.8 ICAT–LC–ESI–MS/MS Kang et al, 2010
A1AT (AP: Protease inhibitor) P01009 Plasma ↑ HCC:CON Disc 24.2% Val 4.8% Disc: 120 HCC, 99 LC, 120 HCON Val: 21 HCC, 6 LC, 18 ASC, 10 HCON HBV/aflatoxin 0.84 QTOF–LC–MS, ELISA Fye et al, 2013
    Plasma ↑ HCC:CON No information *10 HCC; 30 controls (healthy/LC/HBV) HBV 0.92 2.4** Lectin MRM–UPLC–ESI–MS Ahn et al, 2012a, 2012b*
    Serum ↑ HCC:CON No information Disc: 20 HCC, 20 HBV, 20 HCON Val: 20 HCC, 20 HBV, 20 HCON HBV MALDI–TOF–MS/MS, 2DE Feng et al, 2005
A2M (Protease inhibitor) P01023 Plasma ↑ HCC:CON Disc 24.2% Val 4.8% Disc: 120 HCC, 99 LC, 120 HCON Val: 21 HCC, 6 LC, 18 ASC, 10 HCON HBV/aflatoxin 1.13* QTOF–nUPLC–ESI–MS Fye et al, 2013
    Serum ↓ HCC:LC 100% of HCCs Disc: 9 HCC/9 LC Val: 52 HCC/40 LC HBV 0.26 ICAT–LC–ESI–MS/MS Kang et al, 2010
AACT (AP: Protease inhibitor) P01011 Plasma ↑ HCC:CON No information *10 HCC; 30 controls (healthy/LC/HBV) HBV 0.93 3.7** Lectin MRM–UPLC–ESI–MS Ahn et al, 2012a, 2012b*
    Plasma ↑ HCC:CON No information 6 HCC, 3 HCON No information 5.3* 2D LC–MALDI–TOF/TOF Ishihara et al, 2011
AFM (Vitamin transport) P43652 Plasma ↑ HCC:CON No information 6 HCC, 3 HCON No information 33.1 2D LC–MALDI–TOF/TOF Ishihara et al, 2011
    Plasma ↓ HCC:CON No information 28 HCC, 10 HCON No information 0.72 nUPLC–ESI–QTOF–MS and QQQ Lee et al, 2011
Apolipoproteins
Apo A1 (Cholesterol metabolism) P02647 Plasma ↓ HCC:CON Disc 24.2% Val 4.8% Disc: 120 HCC, 99 LC, 120 HCON Val: 21 HCC, 6 LC, 18 ASC, 10 HCON HBV/aflatoxin 0.83 QTOF–nUPLC–ESI–MS Fye et al, 2013
    Serum ↓ HCC:CON 100% of HCCs 20 HCC, 20 HCON No information −3.59* 2DE-coupled MALDI–TOF–MS Sun et al, 2010b
    Serum ↓ HCC:CON 100% of HCCs 8 HCC, 21 HBV, 7 HCON HBV −3.10 2DE-coupled MALDI–TOF–MS Steel et al, 2003
Apo B-100 (Cholesterol metabolism) P04114 Plasma ↓ HCC:CON No information 6 HCC, 3 HCON No information −3.7* 2D LC–MALDI–TOF/TOF Ishihara et al, 2011
Apo L1 (Cholesterol metabolism) O14791 Plasma ↓ HCC:CON No information *10 HCC; 30 controls (healthy/LC/HBV) HBV 0.68 0.5ns Lectin MRM–UPLC–ESI–MS Ahn et al, 2012a, 2012b*
B2M (Immunity) P61769 Plasma ↑ HCC:CON No information 6 HCC, 16 LC/HBV/HCV, 8 HCON HCV/HBV SELDI–TOF–MS Nakatsura, 2010
    Serum ↑HCC:pre-HCC Some Histo. % not stated 38 Pre-HCC; 35 samples upon clinical diagnosis of HCC; 18 samples post treatment (longitudinal collection) HCV 1.82** SELDI–TOF–MS Ward et al, 2006
C4B-α (Complement pathway) P04003 Plasma ↑ HCC:CON Disc 24.2% Val 4.8% Disc: 120 HCC, 99 LC, 120 HCON Val: 21 HCC, 6 LC, 18 ASC, 10 HCON HBV/aflatoxin 1.25ns QTOF–nUPLC–ESI–MS Fye et al, 2013
      ↑ HCC:CON No information *10 HCC; 30 HCON/LC/HBV HBV 0.66 1.3ns Lectin MRM–UPLC–ESI–MS Ahn et al, 2012a, 2012b*
CC3 (Complement pathway) P01024 Plasma ↑ HCC:CON No information 10 HCC; 30 HCON/LC/HBV HBV 0.67 2.0ns Lectin MRM–ESI–UPLC–MS Ahn et al, 2012b
    Plasma ↑ HCC:LC Disc 24.2% Val 4.8% Disc: 120 HCC, 99 LC, 120 HCON Val: 21 HCC, 6 LC, 18 ASC, 10 HCON HBV/aflatoxin 0.70 QTOF–nUPLC–ESI–MS, ELISA Fye et al, 2013
    Serum ↓ HCC:CON 100% of HCCs 8 HCC, 21 HBV, 7 HCON HBV −1.87** 2DE-coupled MALDI–TOF–MS Steel et al, 2003
CC3-α   Serum ↑HCC:CLD/CON No LBs done 45 HCC, 42 CLD, 21 HCON HCV 0.70 SELDI–TOF–MS Kanmura et al, 2010
      ↑HCC:CLD/CON No information 28 HCC, 10 HCON HCV n/r but P of Δ 0.00001 SELDI–TOF–MS, WB Lee et al, 2006
CERU (Cu/ion transport) P00450 Plasma ↑ HCC:CON No information 10 HCC; 30 HCON/LC/HBV) HBV 0.77 1.5** Lectin MRM–UPLC–ESI–MS Ahn et al, 2012b
    Plasma ↑ HCC:CON No information 6 HCC, 3 HCON No information 6.8 2D LC–MALDI–TOF/TOF Ishihara et al, 2011
    Serum HCC only 100% of HCCs 5 HCC, 5 HCON HCV/HBV nanoHPLC–ESI–MS/MS Yang et al, 2007a
    Serum ↑ HCC:CON No information Disc: 20 HCC, 20 HBV, 20 HCON Val: 20 HCC, 20 HBV, 20 HCON HBV 2DE and MALDI–TOF–MS/MS Feng et al, 2005
CLU (apoptosis/complement pathway) P10909 Plasma/serum ↓ HCC:CON No information No information No information SID–MRM–MS Zhao et al, 2010
    Plasma ↓ HCC:CON Disc 24.2% Val 4.8% Disc: 120 HCC, 99 LC, 120 HCON Val: 21 HCC, 6 LC, 18 ASC, 10 HCON HBV/aflatoxin 0.59* QTOF–nUPLC–ESI–MS Fye et al, 2013
    Plasma ↓ HCC:CON No information 10 HCC; 30 HCON/LC/HBV HBV 0.70 0.8ns Lectin MRM–UPLC–ESI–MS Ahn et al, 2012a, 2012b
    Serum ↑ HCC:CON No information Disc: 20 HCC, 20 HBV, 20 HCON Val: 20 HCC, 20 HBV, 20 HCON HBV 2DE and MALDI–TOF–MS/MS Feng et al, 2005
ERBB3 (Signalling pathway) P21860 Serum ↑HCC:LC/CON Disc and Val 1–100% Val 2; Unclear Disc: 10 total, HCC and non-HCC Val 1: 113 HCC, 47 LC, 64 HBV/HCV Val 2: 57 HCC, 35 HBV/HCV HBV/HCV 0.93/0.71 MALDI–TOF–MS, WB, ELISA Hsieh et al, 2011
GFAP (cell differentiation/regeneration) P14136 Serum ↑ HCC:CON 100% HCCs Disc: 20 HCC, 20 HCON Val: 5 HCC, 5 HCON No information 2DE-coupled MALDI–TOF, WB Wu et al, 2012
hCE1 (response to toxins) P23141 Plasma ↑ HCC:CON No information 24 HCC, 14 LC, 7 CH, 8 CCa, 15 stomach cancer, 16 pancreatic cancer No information 0.80 2DE MALDI–TOF/TOF, nano-LC MS/MS, WB Na et al, 2009
HP (AP: Immunity and Fe homoeostasis) P00738 Serum ↑ HCC:CON 100% of HCCs 5 HCC, 5 HCON HCV/HBV 2DE LC–ESI–MS/MS Yang et al, 2007a
    Serum ↑ HCC:CLD 100% of HCCs 56 HCC, 40 CLD No information 0.73 2.57** ELISA Ang et al, 2006
    Serum ↑ HCC:CON No information Disc: 20 HCC, 20 HBV, 20 HCON Val: 20 HCC, 20 HBV, 20 HCON HBV 2DE and MALDI–TOF–MS/MS Feng et al, 2005
    Serum ↑ HCC:CON 100% of HCCs 20 HCC, 20 HCON No information 5.10** 2DE-coupled MALDI–TOF–MS Sun et al, 2010b
    Plasma ↑ CON:LC Disc 24.2% Val 4.8% Disc: 120 HCC, 99 LC, 120 HCON Val: 21 HCC, 6 LC, 18 ASC, 10 HCON HBV/aflatoxin 1.35* QTOF–nUPLC–ESI–MS Fye et al, 2013
HPR (metabolic process) P00739 Serum ↑ HCC:CON 100% of HCCs 5 HCC, 5 HCON HCV/HBV 2DE LC–ESI–MS/MS Yang et al, 2007a
    Plasma ↓ HCC:CON Disc 24.2% Val 4.8% Disc: 120 HCC, 99 LC, 120 HCON Val: 21 HCC, 6 LC, 18 ASC, 10 HCON HBV/aflatoxin 0.65* QTOF–nUPLC–ESI–MS Fye et al, 2013
HPX (Fe homoeostasis) P02790 Plasma ↑ HCC:CON No information 10 HCC; 30 HCON/LC/HBV HBV 0.61 1.2ns Lectin MRM–UPLC–ESI–MS Ahn et al, 2012b
    Plasma ↑ CON:LC Disc 24.2% Val 4.8% Disc: 120 HCC, 99 LC, 120 HCON Val: 21 HCC, 6 LC, 18 ASC, 10 HCON HBV/aflatoxin 0.81 QTOF–nUPLC–ESI–MS Fye et al, 2013
Fu-HPX   Plasma ↑ HCC:CON Some Histo. % not stated 72 HCC, 32 LC, 33 HBV, 133 HCV, 62 other liver diseases, 20 CON HCV/HBV 0.95 1.4** Lectin LC–MS/MS Comunale, 2009
HSP90 (stress response) P08238 Serum ↑ HCC:CON 100% of HCCs 20 HCC, 20 HCON No information 7.04** MALDI–TOF–MS, ELISA Sun et al, 2010b
OPN (biomineralisation/cell adhesion) P10451 Plasma ↑HCC:CLD/CON Val: None Disc: 17 HCC, 18 LC Val: 131 HCC, 76 LC, 52 CHCV/HBV, 53 HCON HCV/HBV 0.76 LC–ESI–MS/MS with 2D nHPLC-coupled LTQ OrbiTrap Shang et al, 2012
    Plasma ↑HCC:CON/LC Some Histo. % not stated 30 HCC, 30 LC, 20 HCON HCV 0.92 4.33 ELISA El-Din Bessa et al, 2010
PON-1 (antioxidant/hydrolase) P27169 Serum ↑ HCC:CON 100% of HCCs 5 HCC, 5 HCON HCV/HBV 2DE LC–ESI–MS/MS Yang et al, 2007a
    Plasma ↓ HCC:CON Disc 24.2% Val 4.8% Disc: 120 HCC, 99 LC, 120 HCON Val: 21 HCC, 6 LC, 18 ASC, 10 HCON HBV/aflatoxin 0.63** QTOF–nUPLC–ESI–MS Fye et al, 2013
Prx-II (antioxidant/oxidoreductase/peroxidase) P32119 Plasma ↑ LC:CON 100% of cases Disc: 27 HBV, 7 HCON Val: 68 HBV, 42 HCON HBV 1.00 MALDI–TOF–MS Lu et al, 2010
    Tissue ↑ HCC:CON 100% of HCCs 6 HCC, 6 non-malignant adjacent tissue HBV 2.1 2DE-coupled MALDI–TOF–MS Matos et al, 2009
SAA (AP and innate response/cell adhesion) P0DJI8 Serum ↑ HCC:CON No information 67 HCC, 53 CHBV, 44 HCON HBV 4.5 2DE MALDI–TOF–MS, SELDI–TOF–MS He et al, 2008
    Serum HCC only 100% of HCCs 5 HCC, 5 HCON HCV/HBV 2DE LC ESI–MS/MS Yang et al, 2007a
SGP-2 (cell death) Q6LDQ3 Serum ↑ HCC:CON 100% HCCs Disc: 20 HCC, 20 HCON Val: 5 HCC, 5 HCON No information 2DE MALDI–TOF–MS, WB Wu et al, 2012
TGM2 (apoptosis/transferase) P21980 Tissue/serum ↑ HCC:CON ALL: 100% of HCCs Tissue disc: 61 HCC, 61 adjacent non-tumour tissue Val: 109 HCC, 42 HCON HBV/HCV LTQ–FT–MS/MS, ELISA Sun et al, 2008
TTR (Transport) P02766 Serum ↓ HCC:CON No information Disc: 20 HCC, 20 HBV, 20 HCON Val: 20 HCC, 20 HBV, 20 HCON HBV 2DE and MALDI–TOF–MS/MS Feng et al, 2005
    Serum ↓ HCC:CON 100% of HCCs 5 HCC, 5 HCON HCV/HBV 2DE LC–ESI–MS/MS Yang et al, 2007a
VIM (host-virus interaction) P08670 Tissue/serum ↑HCC:LC/CON Disc: 100% of HCCs Val: No information Disc (tissue): 40 HCC, 36 CON Val: 88 HCC, 64 CON HBV 0.69 3.27 2DE MALDI–TOF/TOF, ELISA Sun et al, 2010a
VIT (cell adhesion) P04004 Serum ↑ HCC:LC 91% of HCCs 44 HCC, 38 LC No information 0.85 SELDI–TOF–MS Paradis et al, 2005
    Serum ↓ HCC:CON No information 10 HCC, 10 HCON No information SID–MRM–MS Zhao et al, 2010
    Plasma ↑ HCC:CON No information 10 HCC; 30 HCON/LC/HBV HBV 0.54 1.1ns Lectin MRM–UPLC–ESI–MS Ahn et al, 2012b
    Plasma ↓ HCC:CON No information 28 HCC, 10 HCON No information 0.98 nUPLC–ESI–QTOF–MS and QQQ Lee et al, 2011

Abbreviations: 2D=two dimensional; 2DE=two-dimensional electrophoresis; ASC=asymptomatic carrier; AUROC=area under receiver operating characteristics; CCa=cholangiocarcinoma; CHBV/CHCV=chronic HBV or HCV; CLD=chronic liver disease; ELISA=enzyme-linked immunosorbent assay; ESI=electrospray ionisation; HBV=hepatitis B virus; HCC=hepatocellular carcinoma; HCON=healthy control; HCV=hepatitis C virus; Histo=histology; ICAT=isotope-coded affinity tag; LB=liver biopsy; LC=liquid chromatography; MALDI=matrix-assisted laser desorption/ionization; MRM=multiple reaction monitoring; MS=mass spectrometry; n/r=not recorded; nanoHPLC=nano high-performance liquid chromatography; nUPLC=nano ultra-performance liquid chromatography; QQQ=triple quadropole mass spectrometer; qTOF=quadrupole time of flight; WB=western blot; SELDI=surface-enhanced laser desorption/ionization; TOF=time-of-flight. *P<0.05; **P<0.01; ns, non-significant; †, no P-value reported.