SUPPLEMENTARY MATERIAL

Supplementary Table 1. Search history until 23 July 2013
Search / Term / PubMed / ISI Web of Knowledge / EMBASE
1 / colorectal / 97,487 / 210,304 / 130,417
2 / colon / 155,605 / 217,735 / 38,825
3 / rectum / 59,848 / 34,100 / 14,811
4 / 1 or 2 or 3 / 259,912 / 379,653 / 173,157
5 / cancer / 2,823,264 / 2,054,955 / 2,456,953
6 / neoplasm / 2,504,661 / 183,582 / 2,456,953
7 / carcinoma / 678,729 / 909,009 / 597,545
8 / adenoma / 95,852 / 75,381 / 12,669
9 / malignancy / 2,492,704 / 220,272 / 112,603
10 / 5 or 6 or 7 or 8 or 9 / 2,895,665 / 2,586,621 / 2,471,487
11 / autoantibodies / 89,516 / 78,165 / 124,611
12 / antibodies / 829,384 / 1,044,971 / 638,383
13 / 11 or 12 / 834,739 / 1,073,986 / 638,383
14 / detection / 575,884 / 1,318,656 / 602,355
15 / diagnosis / 8,146,349 / 1,367,751 / 3,426,674
16 / 14 or 15 / 8,413,814 / 2,551,321 / 3,812,668
17 / serum / 841,727 / 1,112,335 / 127,602
18 / blood / 3,441,630 / 1,919,250 / 1,082,437
19 / plasma / 702,580 / 1,549,529 / 91,203
20 / 17 or 18 or 19 / 3,967,044 / 3,964,762 / 1,082,437
21 / 4 and 10 and 13 and 16 and 20 / 2,304 / 750 / 439
Supplementary Table 2. Studies assessing blood autoantibodies against TAAs in early detection of colorectal cancer
First author, year / Study population characteristics / Antigen / Sensitivity
(%) / Specificity
(%) / AUC
Country / Cases / Controls / Age range
(cases vs. controls)
(A) Studies detecting autoantibodies based on ELISA
Liu, 2013 [56] / China / 64 CRC / 34 healthy / 28 – 75 y; - / p62 / 23.4 / 97.1 / -
Li, 2012 [66] / China / 70 CRC / 141 healthy / - / IGFBP-2a / 40.0 / 81.0 / 0.67
Chen, 2012 [35] / China / 88 rectum cancer / 300 healthy / 21 – 81 y;
20 – 70 y / AEG-1 / 49.0 / 100.0 / -
Hanafusa, 2012 [36] / Finland / 44 colon cancer / 16 healthy / - / Tektin5 / 9.1 / 100.0 / -
Song, 2011 [74] / South Korea / 50 colon cancer / 50 healthy / - / BCP-20 / 6.0 / 94.0 / -
Kanojia, 2011[32] / India / 54 colon cancer / 50 healthy / - / SPAG9 / 70.0 / 100.0 / -
Wu, 2011[52] / China / 69 CRC / 37 healthy / 21 - 82 y;
18 – 76 y / CEA / 63.8 / 89.2 / -
Chen,2011[60] / China / 220 CRC / 216 healthy / 26 - 95 y;
23 - 85 y / Annexin A / 85.0 / 61.6 / 0.79
Kojima, 2011[39] / Japan / 142 CRC / 150 healthy / 40 – 91 y;
23 – 74 y / p53
CEA / 21.0
9.0 / 93.0
94.0 / 0.56
0.46
Yu, 2011[34] / China / 60 CRC / 400 healthy / - / p53b / 30.0 / 95.0 / -
p53c / 23.3 / 95.25 / -
Wu, 2011 [38] / China / 67 CRC / 400 healthy / 21 – 81 y;
20 – 70 y / p53b / 31.3 / 95.0 / -
p53c / 29.9 / 95.3 / -
Wu, 2010 [24] / China / 66 CRC / 879 healthy / - / p53 / 16.7 / 98.9 / -
Jiang. 2010 [72] / China / 198 colon cancer / 200 healthy / 18 – 90 y;
24 – 76 y / ARD1A / 14.7 / 98.0 / -
Chen, 2010 [20] / China / 232 CRC / 365 healthy / 26 – 95 y;
24 – 84 y / Survivin / 56.9 / 64.1 / 0.62
Chan, 2010 [40] / China / 94 CRC / 54 healthy / 26 – 84 y;
- / CCCAP / 35.1 / 96.3 / -
HDAC5 / 20.2 / 96.3 / -
p53 / 24.5 / 98.1 / -
NY-CO-16 / 18.1 / 100.0 / -
NMDA / 20.2 / 96.3 / -
Above five markers / 58.5 / 92.6 / -
Song, 2009 [75] / USA / 19 colon cancer / 77 healthy / - / Annein A11 / 5.3 / 97.4 / -
Silk, 2009 [58] / USA / 20 CRC / 47 healthy / - / MUC1- IgG / 30.0 / 83.0 / -
MUC1- IgM / 20.0 / 89.4 / -
Kojima, 2009[14] / Japan / 45 CRC / 22 free of cancer / 42 – 85 y;
36 – 82 y / p53 / 20.0 / 100.0 / -
Liu, 2009 [41] / China / 46 colon cancer / 58 healthy / 25 – 76 y;
- / Koc / 15.2 / 100.0 / -
-
-
-
-
-
p62 / 21.7 / 98.3
Imp1 / 21.7 / 100.0
c-myc / 21.7 / 96.6
p53 / 23.9 / 96.6
Above five markers / 60.9 / 89.7
Fujita, 2008 [71] / Japan / 19 colon cancer / 13 healthy / - / HSP70 / 21.0 / 100.0 / -
Suppiah, 2008 [16] / UK / 92 CRC / 28 free of cancer / 63 – 76 y;
65 – 73 y / p53 / 21.7 / 100 / -
Chen, 2007[42] / China / 52 colon cancer / 82 healthy / - / Calnuc / 11.5 / 98.0 / -
-
-
-
-
-
p53 / 9.6 / 98.0
c-myc / 15.4 / 100.0
cyclin B1 / 32.7 / 97.6
cyclin D1 / 21.2 / 98.8
Above five markers / 65.4 / 93.9
Looi, 2006[43] / USA / 57 CRC / 82 healthy / - / p16 / 10.5 / 98.8 / -
-
-
-
c-myc / 14.0 / 100.0
p53 / 8.8 / 98.8
Above three markers / 28.1 / 97.6
Kocer, 2006 [62] / USA / 30 CRC / 22 healthy / 22 – 71 y;
30 – 80 y / MUC5AC / 60.0 / 72.7 / -
Xia, 2005 [73] / USA/
China / 30 CRC / 60 healthy / - / DDX48 / 10.0 / 100.0 / -
Megliorino, 2005 [57] / China / 151 CRC / 82 healthy / - / Survivin / 6.6 / 97.6 / -
Chang, 2005 [44] / China / 167 CRC / 40 healthy / 22 – 85 y;
- / p53 / 28.1 / 100.0 / -
Lechpammer, 2004 [21] / USA / 220 CRC / 42 healthy / 27 – 90 y;
24 – 75 y / p53 / 18.2 / 100.0 / -
(Continued on the following page)
Supplementary Table 2. Studies assessing blood autoantibodies against TAAs in early detection of colorectal cancer (continued)
First author, year / Study population characteristics / Antigen / Sensitivity
(%) / Specificity
(%) / AUC
Country / Cases / Controls / Age range
(cases vs. controls)
Koziol, 2003 [78] / USA
/China / 45 CRC / 346 healthy / - / Seven markers combinationd / 88.0 / 88.0 / -
Shimada, 2003 [46] / Japan / 192 CRC / 205 healthy / - ; 24 – 82 y / p53 / 24.0 / 95.5 / -
Zhang, 2001[55] / China / 65 CRC / 82 healthy / - / p62 / 9.2 / 98.8 / -
-
Koc / 13.8 / 98.8
Zhang, 2003 [45] / China / 45 CRC / 82 healthy / - / c-myc / 4.4 / 100.0 / -
p53 / 17.8 / 97.6 / -
cyclin B1 / 15.6 / 97.6 / -
p62 / 11.1 / 98.8 / -
Koc / 8.9 / 98.8 / -
Imp1 / 13.3 / 97.6 / -
Survivin / 4.4 / 97.6 / -
Above seven markers / 51.1 / 89.0 / -
Tang, 2001 [13] / China / 998 CRC / 211 colorectal polyps / - ;
15 – 88 y / p53 / 13.0 / 99.0 / -
Broll, 2001 [79] / Germany / 130 CRC / 44 healthy / 32 – 92 y;
28 – 83 y / p53 / 15.0 / 100 / -
Albanopoulos, 2000 [53] / Greece / 58 CRC / 28 healthy / 35 – 93 y;
37 – 79 y / CEA IgG / 24.0 / 96.4 / -
CEA IgM / 22.4 / 96.4 / -
CEA IgG/IgM / 32.7 / 96.4 / -
Mosolits, 1999 [12] / Sweden / 1068 CRC / 45 healthy / 32 – 93 y;
37 – 66 y / GA733-2 / 14.5 / 100.0 / -
Syrigos, 1999 [67] / Greece / 55 CRC / 40 healthy / 38 – 78 y;
40 – 76 y / Tropomyosin / 36.3 / 95.0 / -
Hallak, 1998 [49] / Germany / 235 CRC / 194 healthy / p53 / 18.0 / 98.5 / -
Hammel, 1997 [15] / France / 54 CRC / 24 free of cancer / 33 – 90 y;
- / p53 / 26.0 / 100.0 / -
Takahashi, 1995 [69] / Japan/
USA / 160 colon cancer / 40 healthy / - / RAS / 32.0 / 97.5 / -
Konstadoulakis, 1994 [54] / Greece / 25 colon cancer / 28 healthy / - / CEA / 56.0 / 89.4 / -
Kamei, 1992 [70] / Japan / 23 CRC / 45 healthy / - / Histone H2B / 30.3 / 93.3 / -
(B) Studies detecting autoantibodies based on Western blot
Song, 2012 [31] / Korea / 37 colon cancer / 21 healthy / - / CCDC83 / 70.0 / 81.0 / -
Fan, 2011 [61] / China / 86 CRC / 72 healthy / - / SEC61β / 79.0 / 75.0 / 0.80
Chen, 2011 [33] / China / 220 CRC / 63 healthy / - ;
35 – 83 y / RPH3AL / 72.6 / 84.1 / 0.84
Tsunemi, 2010 [11] / Japan / 15 colon cancer / 20 healthy / GRP78 / 20.0 / 100.0 / -
He, 2009 [68] / China / 25 CRC / 15 healthy / 43 – 72 y;
43 – 72 y / IMPDH2 / 32.0 / 100.0 / -
Mueller, 2006 [17] / Germany / 243 CRC / 379 free of cancer and 57 healthy / - / p53 / 28.8 / 100.0 / -
Shebzukhov, 2005 [76] / Russia/
Germany / 194 colon cancer / 100 healthy / - / HDAC3 / 5.2 / 100 / -
Nakamura, 1998 [80] / Japan / 56 CRC / 31 healthy / - / MUC1 / 48.2 / 83.9 / -
Rimm, 1995 [65] / USA / 25 colon cancer / 52 healthy / - / Villin / 44.0 / 90.0 / -
Benmarez, 1990 [51] / France / 44 CRC / 46 healthy / 63 - 76 y; - / c-myc / 56.8 / 83.0 / -
(C) Studies detecting autoantibodies based on spot immunoassay
Scanlan, 2002 [47] / USA / 74 colon cancer / 75 healthy / - / HDAC5 / 2.7 / 100.0 / -
p53 / 14.9 / 100.0 / -
MBD2 / 2.7 / 100.0 / -
TRIP4 / 8.1 / 100.0 / -
NY-CO-45 / 4.1 / 100.0 / -
KNSL6 / 4.1 / 100.0 / -
HIP1R / 6.8 / 100.0 / -
SEB4D / 5.4 / 100.0 / -
KIAA1416 / 5.4 / 100.0 / -
LMNA / 4.1 / 100.0 / -
NY-ESO-1 / 6.8 / 100.0 / -
SSX-2 / 2.7 / 100.0 / -
MAGEA3 / 8.1 / 100.0 / -
(Continued on the following page)
Supplementary Table 2. Studies assessing blood autoantibodies against TAAs in early detection of colorectal cancer (continued)
First author,
year / Study population characteristics / Antigen / Sensitivity (%) / Specificity (%) / AUC
Country / Cases / Controls / Age range
(cases vs. controls)
(D) Studies detecting autoantibodies based on plaque-spot serological assay
Kiyamova, 2012 [63] / Ukraine / 13 colon cancer / 69 healthy / - ;
27 – 62 y / KY-CC-12e / 7.7 / 100.0 / -
KY-CC-25e / 7.7 / 100.0 / -
KY-CC-14e / 7.7 / 100.0 / -
KY-CC-19e / 7.7 / 100.0 / -
KY-THY-16e / 7.7 / 100.0 / -
KY-CC-1e / 39.0 / 70.0 / -
KY-CC-7e / 15.0 / 89.0 / -
1C25e / 15.0 / 85.0 / -
1C21.1e / 46.0 / 22.0 / -
KY-CC-21e / 8.0 / - / -
20 colon cancer / 69 healthy / - ;
27 – 62 y / KY-THY-28e / 39.0 / 78.0 / -
KY-THY-17e / 45.0 / 74.0 / -
KY-THY-22e / 15.0 / 91.3 / -
KY-THY-29e / 15.0 / 91.3 / -
KY-THY-24e / 10.0 / 98.6 / -
(E) Studies detecting autoantibodies based on phage display
Ran, 2008 [27] / China / 24 colon cancer / 24 healthy / 31 – 74 y;
34 – 72 y / Panel of six phage peptides / 83.3 / 87.5 / 0.93
Chang, 2011 [19] / China / 60 CRC / 60 healthy / 30 – 78 y;
30 – 79 y / Panel of five phage peptides / 90.0 / 91.7 / 0.97
Babel, 2011 [26] / Spain / 50 CRC / 46 healthy / 41 – 91 y;
34 – 89 y / SULF1-phage / 50.0 / 73.9 / 0.63
NHSL1-phage / 52.0 / 52.2 / 0.52
MST1-phage / 46.0 / 71.7 / 0.58
GTF2i-phage / 58.0 / 52.2 / 0.60
SREBF2-phage / 48.0 / 60.9 / 0.53
GRN-phage / 58.0 / 58.7 / 0.62
Above six markers / 73.9 / 72.0 / 0.78
(F) Studies detecting autoantibodies based on peptide array
Pedersen, 2013[23] / UK / 97 CRC / 94 healthy / Mean ± SD
65.1 ± 5.8 y;
64.6 ± 5.9 y / p53-4f / 7.2 / 95.0 / 0.53
p53-5f / 13.4 / 95.0 / 0.56
p53-9f / 21.6 / 95.0 / 0.66
p53-10f / 23.7 / 95.0 / 0.63
p53-14f / 6.2 / 95.0 / 0.57
p53-25f / 19.6 / 95.0 / 0.60
p53-26f / 13.4 / 95.0 / 0.55
p53-27f / 9.3 / 95.0 / 0.56
p53-34f / 11.3 / 95.0 / 0.60
p53-39f / 4.1 / 95.0 / 0.51
p53-41f / 5.2 / 95.0 / 0.56
p53-42f / 11.3 / 95.0 / 0.50
p53-43f / 13.4 / 95.0 / 0.59
p53-44f / 14.4 / 95.0 / 0.58
p53-45f / 7.2 / 95.0 / 0.56
p53-58f / 13.4 / 95.0 / 0.57
p53-59f / 8.2 / 95.0 / 0.52
p53-78f / 20.6 / 95.0 / 0.55
Pedersen, 2011 [18] / USA / 58 CRC / 53 healthy / Mean ± SD
60.3 ± 7.5 y;
46.4 ± 6.4 y / MUC1 / 6.9 / 90.1 / -
MUC1 6Tng / 20.7 / 90.1 / -
MUC1 9Tng / 20.7 / 90.1 / -
MUC1 15Tng / 32.8 / 90.1 / -
MUC1 9Core3g / 27.6 / 90.1 / -
MUC1 15Core3g / 44.8 / 90.1 / -
MUC1 9STng / 39.7 / 96.2 / -
MUC1 15STng / 56.9 / 96.2 / -
Tn-MU4-1-Tn-MUC4-5g / 37.9 / 96.2 / -
Tn-MU4-6-Tn-MUC4-20g / 29.3 / 92.4 / -
Tn-MU4-5g / 15.5 / 90.1 / -
All Tn-MUC4g / 53.4 / 89.7 / -
recMUC4g / 13.8 / 96.1 / -
Tn-recMUC4g / 37.9 / 86.8 / -
(Continued on the following page)
Supplementary Table 2. Studies assessing blood autoantibodies against TAAs in early detection of colorectal cancer (continued)
First author,
year / Study population characteristics / Antigen / Sensitivity
(%) / Specificity
(%) / AUC
Country / Cases / Controls / Age range
(cases vs. controls)
(G) Studies detecting autoantibodies based on protein array
Nam, 2003 [64] / USA / 43 colon cancer / 15 healthy / - / UCHL3 / 44.2 / 100 / -
Babel, 2009 [25] / Spain / 52 CRC / 42 healthy / 51 – 91 y;
- / ACVR2B / 59.6 / 76.2 / 0.67
Pim-1 / 48.1 / 83.3 / 0.65
MAPKAPK3 / 72.7 / 74.0 / 0.73
Above 3 markers / 84.4 / 71.4 / 0.85
(H) Studies detecting autoantibodies based on immunofluorometric assay
Angelopoulou, 1994 [50] / Canada / 82 colon cancer / 150 healthy / - / p53 / 15.8 / 99.3 / -
(I) Studies detecting autoantibodies based on PARSE
Xu, 2012 [77] / China / 48 CRC / 46 healthy / - / KRT20 / 0 / 100.0 / -
MMP3 / 0 / 100.0 / -

Abbreviations: ACVR2B, Activin receptor type-2B; ANXA A4, Annexin A4; AUC, area under the receiver operating characteristic curve; AEG-1, Astrocyte elevated gene-1; ARD1A, Human arrest defective 1; CCCAP, Centrosomal colon cancer autoantigen protein; DDX48, DEAD-box protein 48; GRN, Granulin; GRP78; 78 kDa glucose-regulated protein, GTF2i, General transcription factor II i; HDAC3, Histone deacetylase 3; Hsp 70, Heat shock protein 70; IGFBP-2, Insulin-like growth factor-binding protein-2; IMPDH2, Inosine monophosphate dehydrogenase II; MAGEA3, Melanoma-associated antigen 3; MAPKAPK3, Mitogen-activated protein kinase-activated protein kinase; MST1, Mammalian STE20-like protein kinase 1; NHSL1, NHS-like protein 1; NMDA, Glutamate binding subunit of the NMDA receptor; PARSE, proteinA/G–based reverse serological evaluation; RPH3AL, Rabphilin-3A-like protein; SEC61β, Transport protein Sec61 subunit beta; SEN, sensitivity; SPAG9, Sperm-associated antigen 9 gene; SPE, specificity; SREBF2, Sterol regulatory element binding protein 2; SULF1, Sulfatase 1; TEKT5, Tektin protein 5; UCHL3, Ubiquitin carboxyl-terminal hydrolase isozyme L3

a: Results were only available for cases in stage I and II.

b: Result of p53-ELISA test

c: Result of phage-ELISA test

d: The combination includes antibody marker of c-myc, cyclin B1, IMP1, Koc, p53, p62, and survivin.

e: Clone number of the marker, detailed information can be found on the website of Cancer Immunome Database (http://ludwig-sun5.unil.ch/CancerImmunomeDB/)