Table 4. Serum markers in CCA.
| Markers | Specificity | Sensitivity | Notes | |
|---|---|---|---|---|
| Diagnostic markers | CA19-9 | 67%-98% | 38%-93% | |
| CEA | 50%-87.8% | 33%-84% | ||
| Interleukin-6 | low | 100% | ||
| CYFRA 21-1 and MMP-7 | low | Variable, depending on the cut-off value | Using CYFRA 21-1 and MMP-7 with CEA and CA19-9 demonstrated the highest diagnostic accuracy of 93.9%[ | |
| SSP411 | Elevated in the bile of CCA patients and recently found to successfully distinguish CCA from choledoco-lithiasis as a single serum-based biomarker | |||
| miRNA | CCA-specific miRNA expression profiles has been identified: miR-125a, -31, and -95 are downregulated, while multiple miRNAs are upregulated as compared to nonmalignant cholangiocytes. Low specificity of single mi-RNA suggests that the most effective use of miRNAs is likely as multimarker panels specific for CCA | |||
| CTC | 17%-23% (Using a cut-off of 2 CTCs/7.5 mL of peripheral blood) |
More useful as prognostic markers, correlating with poor overall survival | ||
| Prognostic markers | miRNA multi-marker panels | Correlation with overall survival and rate of metastasis | ||
| EGFR | Over-expression of EGFR is prognostic of decreased overall survival | |||
| CYFRA 21-1 | values above 2.7-3 ng/mL is prognostic of decreased overall survival | |||
| Theranostic markers | EGFR mutations | In a phase II study of single agent erlotinib in patients with advanced biliary cancer, stable disease was reached in 17% of patients | ||
| Upregulation of vascular endothelial growth factor (VEGF) | It is associated with an EGFR inhibitor-resistant phenotype. Vandetanib, a dual inhibitor of VEGF and EGFR, has shown prolonged time to metastasis in CCA tumors that harbor both mutations | |||
| KRas/BRAF mutations | Several studies suggest the potential application for targeted therapy with vemurafenib in this population, but not with EGFR-inhibitor | |||
| HER2 overexpression | This 4%-5% of CCA may benefit from targeted anti-HER2 therapy | |||
| Expression of miRNAs | The increased expression of miRNAs predicts a favorable response to gemcitabine treatment. Moreover, treatment of cholangiocytes with miR-494, which is down-regulated in CCA, induced cell-cycle arrest in tumor cells while sparing normal cells |