Table 3.
Studies of antibodies analyzed in pre-diagnostic blood samples (collected in prospective cohort or general screening settings) for the purpose of risk prediction or early diagnosis of colorectal cancer.
| Reference | Cohort (Design) |
Time from Sampling to Diagnosis (Cohort Setting Only) |
CRC | Adenoma | Contr./ Cohort |
Biomarker/ Platform |
Main Findings | Adapted NOS Scale ** Max: Selection = ★★★★ Comp. = ★★ Exp./Outc. = ★★★ |
|---|---|---|---|---|---|---|---|---|
| Cohort setting | ||||||||
| Pedersen et al. Int J Cancer, 2014 [63] |
UKCTOCS (Nested case control) | 6.8 years (median) | 97 | - | 94 * | Autoantibodies: MUC1, MUC2 and MUC4 |
Top markers: MUC1-STn, MUC1-Core3 MUC1-STn Sensitivity: 8.2% Specificity: 95% MUC1-Core3 Sensitivity: 13.4% Specificity: 95% |
★★★★ ★ ★★★ |
| Butt et al. Cancer Epidemiol Biomarkers Prev, 2018 [60] |
CLUE, CPSII, HPFS, MEC, NHS, NYUWHS, PHS, PLCO, SCCS and WHI (Nested case control) | 4–18 years (median, different studies) | 4210 | - | 4210 * | Antibody responses to 9 Streptococcus gallolyticus (SGG) proteins | Top marker: Gallo2178 Gallo2178 All cases: OR: 1.23 (95% CI: 0.99–1.52) Diagnosed <10 years after blood draw: OR: 1.40 (95% CI: 1.09–1.79) |
★★★ ★★ ★★★ |
| Teras et al. Cancer Epidemiol Biomarkers Prev, 2018 [64] |
CPSII (Nested case control) | 11 years (follow up) | 392 | - | 774 * | p53 autoantibodies | All cases: RR: 1.77 (95% CI: 1.12–2.78) Diagnosed <3 years after blood draw: RR: 2.26 (95% CI: 1.06–4.83) |
★★★★ ★★ ★★★ |
| Butt et al. Cancer Epidemiol Biomarkers Prev, 2020 [61] |
CLUE, CPSII, HPFS, MEC, NHS, NYUWHS, PHS, PLCO, SCCS and WHI (Nested case control) | 7 years (median) | 3702 | - | 3702 * | p53 autoantibodies | All cases: OR: 1.33 (95% CI: 1.09–1.61) Diagnosed <4 years after blood draw: OR: 2.27 (95% CI: 1.62–3.19) |
★★★ ★★ ★★★ |
| Screening setting | ||||||||
| Chen H et al. Oncotarget, 2016 [62] |
BliTz (validation study) |
- | 49 | AA: 99 NAA: 29 |
100 | Autoantibodies to 64 tumor associated antigens Tested: individual proteins and 2- to 6-marker panels |
Top hits: TP53, anti-IMPDH2, anti-MDM2, anti-MAGEA4 Best 2-marker panel (TP53, anti-IMPDH2): sensitivity CRC 10% (4–22), sensitivity AA 7 (3–14), specificity 95 (89–98) Best 6-marker panel (TP53+IMPDH2+MDM2 +MAGEA4+CTAG1 +MTDH), Sensitivity CRC 24% (15–38), sensitivity AA 25% (18–35), specificity 85% (77–91) |
★★★★ - ★★★ |
Abbreviations (not including biomarker names, for which the reader is referred to the original study article): AA, advanced adenoma; BliTz, Begleitende Evaluierung innovativer Testverfahren zur Darmkrebs-Früherkennun, Germany; CLUE, Campaign Against Cancer and Stroke; CPSII, Cancer Prevention Study-II; CRC, colorectal cancer; EPIC, European Prospective Investigation into Cancer and Nutrition; HPFS, Health Professionals Follow-up study; MEC, Multiethnic Cohort Study; NAA, non-advanced adenoma, NHS, Nurses’ Health Study; NYUWHS, NYU Women’s Health Study; OR, odds ratio; PHS, Physicians’ Health Study; PLCO, Prostate, Lung, Colorectal, and Ovarian Screening Study; SCCS, Southern Community Cohort Study; UKCTOCS, UK Collaborative Trial of Ovarian Cancer Screening; WHI, Women’s Health Initiative. * Matched controls. ** Newcastle–Ottawa Quality Assessment Scale for case-control studies, adapted for use for assessment of biomarker studies conducted in a screening setting. For case-control studies: selection (max 4 stars), comparability (max 2 stars), exposure (max 3 stars). For cohort studies: selection (max 4 stars), comparability (max 2 stars), outcome (max 3 stars).