Table 4.
Summary of results of associations between tumour and self-reactive antibodies and site-specific cancer risk, in the general population. The evidence of association is defined by the number of studies reporting on the association, the range of the hazard ratio/odds ratio/relative risks/standardized incidence ratio reported in each study, and the statistical significance.
| Cancer type | Serum Antibodies | Main findings | Diagnostic potential |
|---|---|---|---|
| All/any | Anti-p53 | Positive association | NA |
| Anti-phospholipid | Possible inverse association | NA | |
| Breast | Antibodies to six autoantigens: p53, c-myc, HER2, NY-ESO-1, BRCA2 and MUC1 (assessed individually) |
Positive association for the presence of 1 or more of listed autoantibodies | Autoantibody panel likely to perform better than single marker – but not assessed |
| Anti-thyroid peroxidase | Inverse association | NA | |
| Colorectal | Anti-p53 | Positive association | High specificity but low sensitivity |
| Anti-Neu5Gc (antibodies to meat-derived antigens) | Positive association for total anti-Neu5Gc IgG; Single epitopes no association | NA | |
| IGFBP-2 IgG | Positive association | AUC = 0.92 (when combined with serum IGFBP-2 levels) | |
| Multiple TAA antibodies (8000 potential antigens) |
Positive association: MAPKAPK3, PIM1, STK4, SRC, and FGFR4 Negative association: ACVR2B |
Specificity and sensitivity high for anti-ACVR2B, anti-MAPKAPK3, anti-PIM1 combined | |
| Anti-ASXL2* | Positive association | AUC = 0.67 | |
| Oesophageal | Anti-ASXL2* | Positive association | AUC = 0.76 |
| Anti-p53 | Positive association | NA | |
| Gastric | Panel; p62, c-Myc, NPM1, 14-3-3ξ, MDM2 and p16 | Positive associations | Selected six panel for testing |
| Glioma | Anti-IGFBP-2 | Positive association for astrocytoma | AUC = 0.80 (when combined with serum IGFBP-2 levels) |
| Hepatocellular carcer | Multiple TAA antibodies | Positive associations for autoantibodies to calreticulin, cytokeratin 8, nucleoside diphosphate kinase A, F1-ATP synthase | NA |
| Multiple antibodies | Positive association for antibodies to 21 TAAs; (best performers: IMP-1, KOC, p53 and c-myc, Sui1 and RalA, Calreticulin, and HCC1) | Moderate sensitivity high specificity | |
| 12 antibody panel | Positive association for autoantibodies to HCC1, P16, P53, P90, and Survivin | NA | |
| Lung cancer/NSCLC | Panel: p62, BIRC, Livin-1, p53, PRDX, NY-ESO-1 and Ubiquitin | Positive association | AUC = 0.81 |
| Panel: p53, c-myc, HER2, NY-ESO-1, CAGE, MUC1 ans GBU4-5 | Positive association | High sensitivity for squamous cell lung cancer, moderate sensitivity for all lung cancers | |
| Panel: GAGE7, CAGE, MAGEA1, SOX2, GBU4-5, PGP9.5, and p53 | Positive association | Moderate sensitivity and specificity | |
| Multiple antibodies: (212 selected from immunogenic tumour expressed proteins) |
Positive association for the 5 most immunogenic combined | High sensitivity and specificity | |
| Multiple autoantibodies: p62, p16, Koc, p53, Cyclin B1, Cyclin E, Survivin, HCC1, and RalA | Strongest serological response: Survivin, Cyclin B1, HCC1, and p53 | Low to moderate potential as individual autoantibodies | |
| Anti-BARD1 | Positive association | High sensitivity and specificity | |
| Brain protein autoantibodies | Possible positive association | NA | |
| CD25 and FoxP3 IgGs | Positive association for CD25a; weaker for FoxP3 | NA | |
| Mesothelioma | Panel including PDIA6, MEG3, SDCCAG3, IGHG3, IGHG1 | Positive association | High specificity and sensitivity |
| Anti-p53 | No association |
NA |
|
| Lymphoma/NHL | Anti-cyclic citrullinated peptide (CCP) | No association | NA |
| Autoimmune diseases No individual autoantibodies specified |
Positive association | NA | |
| Ovarian cancer | Panel: anti- MDM2, PLAT, NPM1, 14-3-3 Zeta, p53, and RalA | Positive association | High specificity and sensitivity |
| Anti-MUC1, anti-CA125 | Positive association | NA | |
| Anti-MUC1 | Indirect evidence for inverse association | NA | |
| Anti-p53 and anti-SBP-1** | Positive association for serous ovarian cancer | High specificity and sensitivity for CA125, anti-TP53, and anti-SBP1 combined (AUC 0.96) | |
| Anti-HE4 | Positive association | NA | |
| Pancreatic | Anti-Ezrin | No association | NA |
| Bladder | Anti-UPII | Positive association |