Table 1.
Established and potential biomarkers in CRC diagnosis.
| References | Biomarker | Specimen | Test | Accuracy | Regulatory status |
|---|---|---|---|---|---|
| miRNAs | |||||
|
Ng et al. (2009)
Uratani et al. (2016) Yau, Tang, Harriss, Dickins, and Polytarchou (2019) |
miR-92a | Blood | NA | CRC: AUROC: 0.89 (plasma) Sensitivity: 0.89 Specificity: 0.70 A: AUROC: 0.75 (serum) Sensitivity: 0.65 Specificity: 0.79 AA: AUROC: 0.84 (serum) |
– |
| Stool | NA | CRC: AUROC: 0.80 Sensitivity: 0.47 Specificity: 0.91 A: AUROC: 0.64 Sensitivity: 0.43 Specificity: 0.91 |
– | ||
|
Peng et al. (2017)
Toiyama et al. (2013) Yau et al. (2019) |
miR-21 | Blood | NA | CRC: AUROC: 0.85 (plasma)/0.87 (serum) Sensitivity: 0.69/0.75 Specificity: 0.86/0.84 A: AUROC: 0.80 (serum) Sensitivity: 0.77 Specificity: 0.81 |
– |
| Stool | NA | CRC: AUROC: 0.84 Sensitivity: 0.60 Specificity: 0.86 A: AUROC: 0.77 Sensitivity: 0.60 Specificity: 0.83 |
– | ||
| Yau et al. (2019) | 2-miRNA panel: miR-92 miR-21 |
Stool | NA | CRC: AUROC: 0.84 Sensitivity: 0.54 Specificity: 0.88 |
– |
| Duran-Sanchon et al. (2020) | GBM modela: miR-421 miR-27a-3p |
Stool | NA | CRC and AA: AUROC: 0.74 (training set)/0.63 (test set) Sensitivity: 0.74/0.67 Specificity: 0.63/0.60 CRC: AUROC: 0.86/0.74 Sensitivity: 0.96/0.96 Specificity: 0.36/0.33 AA: AUROC: 0.71/0.64 Sensitivity: 0.61/0.59 Specificity: 0.71/0.69 |
– |
| Liu, Klein, et al. (2018) and Liu, Liu, et al. (2018) | 4-miRNA panel: miR-21 miR-92a miR-29a miR-125b |
Blood (serum) | NA | CRC: AUROC: 0.95 Sensitivity: 0.85 Specificity: 0.99 |
– |
| Chang et al. (2016) | 2-miRNA panel: miR-223 miR-92a |
Blood (plasma) | NA | CRC: AUROC: 0.91 Sensitivity: 0.97 Specificity: 0.75 |
– |
| Herreros-Villanueva et al. (2019) | 6-miRNA panel: miR-19a miR-19b miR-15b miR-29a miR-335 miR-18a |
Blood (plasma) | NA | CRC and AA: AUROC: 0.92 Sensitivity: 0.85 Specificity: 0.90 |
– |
| Sazanov, Kiselyova, Zakharenko, Romanov, and Zaraysky (2017) | 2-miRNA panel: miR-21 miR-92a |
Saliva | NA | CRC: Sensitivity: 0.97 Specificity: 0.91 |
– |
| Rapado-González et al. (2019) | 5-miRNA panel: miR-186-5p miR-29a-3p miR-29c-3p miR-766-3p miR-491-5p |
Saliva | NA | CRC: AUROC: 0.75 Sensitivity: 0.72 Specificity: 0.67 |
– |
| DNA methylation | |||||
| Church et al. (2014) | SEPT9 | Blood (plasma) | Epi proColon | CRC: Sensitivity: 0.68 Specificity: 0.79 AN: Sensitivity: 0.25 Specificity: 0.79 AA: Sensitivity: 0.22 Specificity: 0.79 |
Registered trademark. FDA approval: alternative for CRC screeningb |
|
Baek et al. (2009)
Carmona et al. (2013) Chen et al. (2005) Fu et al. (2018) Itzkowitz et al. (2007) Kisiel et al. (2013) Li et al. (2009) Lu et al. (2014) |
VIM | Blood (plasma) | NA | CRC: Sensitivity: 0.59 Specificity: 0.93 |
– |
| Stool | ColoSure | CRC: Sensitivity: 0.81 Specificity: 0.95 |
Trademark. Not FDA approval | ||
| Jung et al. (2020) | SFRP2 | Blood (plasma and serum) | NA | CRC: Sensitivity: 0.64–0.67 Specificity: 0.97–1.00 A: Sensitivity: 0.06–0.81 Specificity: 0.73–1.00 |
– |
| Stool | NA | CRC: Sensitivity: 0.56–0.94 Specificity: 0.77–0.97 A: Sensitivity: 0.28–0.76 Specificity: 0.55–1.00 |
– | ||
| Luo et al. (2020) | cd-score (multi-region panel) | Blood (plasma) | NA | CRC: AUROC: 0.96 Sensitivity: 0.88 Specificity: 0.90 |
– |
| Luo et al. (2020) | cg10673833 (single probe) | Blood (plasma) | NA | CRC: AUROC: 0.90 Sensitivity: 0.90 Specificity: 0.87 |
– |
| Kandimalla et al. (2020) | Multi-region panel | Blood (plasma) | EpiPanGI-Dx | CRC: AUROC: 0.98 |
– |
| ColonES Product Sheet (2020) | Multi-region panel | Blood (plasma) | ColonEs | CRC and A: Sensitivity: 0.91 (A)/0.97 (I)/0.94 (II–IV) Specificity: 0.99 |
– |
| Multi-modal | |||||
| USPSTF. US Preventive Services Task Force et al. (2020) | Multi-modal panel: KRAS mutations (×7) NDRG4 m.s. BMP3 m.s. FIT |
Stool | Cologuard | CRC: Sensitivity: 0.93 Specificity: 0.85 AN: Sensitivity: 0.47 Specificity: 0.89 AA: Sensitivity: 0.43 Specificity: 0.89 |
Registered trademark. FDA approval: CRC screeningc |
| Friedland et al. (2020) | Multi-modal panel: Circulating GI endothelial cells Somatic mutationsd SEPT9 m.s. |
Blood | FirstSight | CRC: Sensitivity: 1.00 Specificity: 0.90 AA: Sensitivity: 0.80 |
Trademark |
| Cohen et al. (2018) | Multi-modal panele: 8 proteins Mutations |
Blood (plasma) | CancerSEEK | CRC: AUROC: 0.85 |
– |
| Duran-Sanchon et al. (2020) | GBM modela: miR-421 miR-27a-3p FIT |
Stool | NA | CRC and AA: AUROC: 0.72 (training set)/0.70 (test set) Sensitivity: 0.74/0.68 Specificity: 0.63/0.64 CRC: AUROC: 0.90/0.93 Sensitivity: 0.96/0.97 Specificity: 0.36/0.43 AA: AUROC: 0.70/0.64 Sensitivity: 0.61/0.49 Specificity: 0.71/0.71 |
– |
| Metabolomic | |||||
| Deng et al. (2017) | Metabolites: Succinic acid Ascorbic acid Carnitine |
Urine | PolypDx | HP and A: Sensitivity: 0.43 Specificity: 0.91 |
Trademark. Available for CLIA-certified laboratories |
a
miRNA-based predictive model included miR-421 and miR-27a-3p, along with age and sex.
b
Alternative in average-risk individuals who refuse other screening modalities.
c
CRC screening in average-risk population.
d
Somatic mutations in oncogenes and tumor suppressor genes.
e
8 proteins (cancer antigen 125, carcinoembryonic antigen, cancer antigen 19–9, proactin, hepatocyte growth factor, osteopontin, myeloperoxidase, and tissue inhibitor of metalloproteinases 1) and mutations (SNVs or INDELs) in 1933 distinct genomic positions.
Abbreviations: A, adenoma; AA, advanced adenoma; CRC, colorectal cancer; AN, advanced neoplasia; AUROC, area under the receiver operating characteristic curve; CLIA, Clinical Laboratory Improvement Amendments; FIT, fecal immunochemical test; GBM, gradient boosting machine; GI, gastrointestinal; HP, hyperplastic polyp; m.s., methylation status; NA, not available.