Table 3.

Summary of blood/serum biomarkers

Number of participants included
Author + dateJournalMethodMarkerMechanismNCAdenomaColorectal cancerSensitivity (%)95% CISpecificity (%)95% CI
1. Serum/plasma DNA biomarkers
 Pack 2013 (36)Int J Colorectal DisMSP-SSCPE cadherinDNA hypermethylation604060CRC 60NS84NS
StageStage I 4887
I/II/III/IV
APC14/14/28/4CRC 57NS86NS
Stage I 5789
SMAD4CRC 52NS64NS
Stage I 4787
DAPK1CRC 50NS74NS
Stage I 4370
FHITCRC 50NS84NS
Stage I 2967
 Lange 2012 (37)PLos ONEMethylightTHBD-MDNA hypermethylation980106CRC 71NS80NS
StageStage I/II 74
I/II/III/IV
28/30/45/3NS
C9orf50-MNS
 Cassinotti 2012 (38)Int J CancerMS-PCR6 Gene panel - CYCD2, HIC1, PAX 5, RASSF1A, RB1, SRBCDNA hypermethylation303030CRC 83.771–9767.951–85
18 Ad >1 cmStageAd 54.637–7264.547–82
I/II
11/19
 Warren 2011 (39)BMC MedQRT-PCRSEPT9DNA hypermethylation94050CRC 9077–968880–94
Stage
I/II/III/IV
71/90/100/100
Stage I + II 86.871–95
 Tanzer 2010 (40)PLoS ONEQRT-PCRALX4 +SEPT9DNA hypermethylation22495Precancerous Colorectal lesion 7130–959575–99
36 adStage
13 HPI/III
4/1
 Lee 2009 (41)Clin Cancer ResMS-PCR4 gene panel - APC, MGMT, RASSF2A, Wif-1DNA hypermethylation27664243CRC 86.582–9192.188–95
Stage
I/IIAd 74.763–8591.386–95
44/199
 Lofton-Day 2008 (42)Clin ChemQRT-PCRTMEFF2DNA hypermethylation1850135CRC 3095
NGFRCRC 33NS95NS
SEPT9CRC 5295
 Han 2008 (43)Clin Cancer ResQRT-PCR5 gene panel - CDA, MGC20553, BANK1, BCNP1, MS4A1DNA hypermethylation5705894NS77NS
2. Blood/serum RNA biomarkers
 Wang 2012 (44)PLoS ONEQRT-PCRmiR601RNA expression584390CRC 69.2NS72.467–83
StageAd 72.151.7
I/II/III/IV
miR76026/25/29/10CRC 80NS72.471–86
Ad 69.862.1
miR760 + miR 29a + miR92aCRC 83.3NS93.191–98
 Kanaan 2012 (45)Ann SurgQRT-PCRmiR21Tumor-associated RNA expression20020CRC 90NS90NS
 Huang 2010 (46)Int J CancerQRT-PCRmiR29aTumor-associated RNA expression5937100CRC 6989.1
StageAd 62.284.7
I/II/III/IV
miR92a27/25/38/10CRC 84NS71.2NS
Ad 64.981.4
miR29a + miR92aCRC 8384.7
Ad 7379.7
 Ng 2009 (47)GutQRT-PCRmiR92Tumor-associated RNA expression69090CRC 8970
StageNSNS
miR17-3pI/II/III/IVCRC 6470
6/34/23/27
3. Blood/serum protein assay biomarkers
 Wilson 2012 (48)British J CancerELISAMMP9Over expression of proteolytic enzymes52512546CRC 79NS70NS
 Liu 2011 (49)Int J Med SciMALDI-TOFMS4 molecular weights 2870.7, 3084, 9180.5, 13748.8Protein finger-printing1200144CRC 92.85NS91.25NS
Dukes
A/B/C/D
28/6/23/27
 Chen 2011 (50)Clinic Chim ActaWestern BlotRPH3AL auto-antibodiesAuto-antibodies targeting tumor-associated antigens63084CRC 72.6NS84.1NS
Dukes
A+B/C+DDuke A+B 64.7
34/50
Dukes C+D 78
 Mead 2011 (51)Br J CancerELISALinel 79bp, Alu 247bp, Alu 115bp, Mitochondrail DNAMitochondrial and small DNA fragments352624CRC 83NS72NS
 Babel 2011 (52)Mol Cell ProteomicsELISASULF1Auto-antibodies targeting tumor-associated antigens103050CRC 73.950
NHSL1CRC 52.252
MST1CRC 71.746
GTF2iCRC 52.2NS58NS
SREBF2CRC 60.948
GRNCRC 58.758
6 CombinedCRC 73.972
 Pederson 2011 (53)Int J CancerELISAMUC1 + MUC4Auto-antibodies with altered glycosylation and expression53058CRC 79NS92NS
 Tagi 2010 (54)J GastroeneterolELISA4 protein panel - DK-BLY, CEA, Ca 19-9, S-p53Aberrantly expressed protein isoforms250130CRC 60.6NS80.0NS
 Mroczko 2010 (55)Int J Colorectal DisELISAMMP9Proteolytic enzyme degradation703575CRC 55
Duke
TIMP-1A/B/C/DCRC 61
0/28/27/20NS100
MMP9+TIMP-1CRC 75
MMP9 + CEACRC 75
 De Chiara 2010 (56)BMC CancerELISAsCD26Diminished protein expression6810833CRC 81.865–9379.468–88
48 Ad >1 cmDuke
40 Ad <1 cmA/B/C/DCRC+ Ad 5847–6975.569–81
18 HP1/12/15/4
 Kim 2009 (57)J Proteome ResWestern BlotS100A8Over expression of proteins in cancer tissue211177CRC 4195
StageAd+ Stage I CRC 3295
S100A9I/II/III/IVCRC 4495
14/23/21/19Ad + Stage I CRC 40NS95NS
CEACRC 22100
Ad + Stage I CRC 21100
 Fentz 2007 (58)Proteomics Clin ApplSELDI-TOF-MSTransthyretinAuto-antibodies targeting tumor-associated antigens585854CRC 60.7100
All stage IIIAd 85.767.8
C3a-desArgCRC 60.7NS92.5NS
Ad 78.577.5
Transthyretin + C3a-desArgCRC 60.7100
Ad 96.470.3
4. Other blood/serum biomarkers
 Bellows 2011 (59)Canc Epidemiol Biomarkers PrevFlow cytometryMSCsCirculating progenitor cells260456473
CPCsStage5158
LCsI/II/III/IV71NS81NS
ECs2/8/11/243870
CD34 bright cells7766

Abbreviations: Ad, adenoma; CRC, colorectal cancer.