| Biomarker | cfDNA (cell-free DNA) | Full name | Cell-free DNA | Molecular Type | Nucleic acids (fragments of DNA) |
| Molecular Formula | Molecular Weight | 150-200 bp | Core Functional Dimensions | Diagnosis and Prognosis | |
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA, eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Plasma/bile (NGS, methylation sequencing) | ||
| Pathobiological Mechanisms | It contains tumor-derived ctDNA, reflecting the overall genomic characteristics of the tumor; Aberrant methylation is tumor specific | ||||
| Clinical Availability Status | Study validation; Methylation detection can improve the efficiency of early diagnosis | ||||
| Notes and Dynamics | cfDNA methylation panels (such as OPCML and HOXD9) had a specificity of 100% in differentiating CCA from benign biliary diseases. Early detection sensitivity 76%, specificity 94% RRBS techniques | ||||
| Biomarker | ctDNA (Circulating Tumor DNA) | Full name | Circulating tumor DNA | Molecular Type | Nucleic acid (fragments of DNA) |
| Molecular Formula | Molecular Weight | 150-200 bp | Core Functional Dimensions | Diagnosis, prognosis, treatment response monitoring, MRD monitoring | |
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA, eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Plasma/bile (NGS, ddPCR, dPCR) | ||
| Pathobiological Mechanisms | Tumor cells are released by apoptosis/necrosis, carrying tumor-specific mutations and abnormal methylation, reflecting tumor heterogeneity | ||||
| Clinical Availability Status | Research/clinical monitoring tools; In multi-center validation | ||||
| Notes and Dynamics | Bile ctDNA detection sensitivity (96.2%) and drivers mutation detection rate (54%) is significantly higher than the plasma (31.6%, 17%); VAF > 3.9% tip poor prognosis (OS 4.9 months) | ||||
| Biomarker | RET (fusion) | Full name | Rearranged during transfection fusions | Molecular Type | Nucleic acids (DNA synthesis) |
| Molecular Formula | Targeted therapy options | Molecular Weight | Core Functional Dimensions | ||
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA, eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Tissue/Plasma (NGS) | ||
| Pathobiological Mechanisms | Fusions activate RET signaling and promote tumor proliferation and angiogenesis | ||||
| Clinical Availability Status | The validation; Some patients carry | ||||
| Notes and Dynamics | |||||
| Biomarker | NTRK (fusion) | Full name | Neurotrophic tyrosine receptor kinase fusions | Molecular Type | Nucleic acid (DNA fusion) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Targeted therapy options | ||
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA, eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Tissue/Plasma (NGS) | ||
| Pathobiological Mechanisms | Fusion activates the TRK signaling pathway and promotes tumor growth | ||||
| Clinical Availability Status | Clinical validation (tumor-agnostic therapy); Rare (<1%) | ||||
| Notes and Dynamics | Larotrectinib, entrectinib approved, ORR 75%; ctDNA testing can assist in screening patients and avoid invasive biopsy | ||||
| Biomarker | BRAF V600E (mutation) | Full name | B-Raf proto-oncogene, serine/threonine kinase V600E mutation | Molecular Type | Nucleic acids (DNA mutations) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis and targeted treatment options | ||
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Organization/plasma (NGS, ddPCR) | ||
| Pathobiological Mechanisms | Mutations activate the MAPK pathway and promote tumor proliferation and invasion | ||||
| Clinical Availability Status | Clinical validation; About 3% of patients with iCCA carry it | ||||
| Notes and Dynamics | dabrafenib+trametinib (ORR 47%) for patients without other treatment options; Tumor-agnostic therapy was indicated | ||||
| Biomarker | FGFR2 (fusion/rearrangement) | Full name | Fibroblast growth factor receptor 2 fusions | Molecular Type | Nucleic acid (DNA fusion) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis, targeted therapy selection, prognosis | ||
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Tissue/plasma/bile (NGS, FISH) | ||
| Pathobiological Mechanisms | Fusion activation FGFR signaling pathways, and promote the tumor proliferation and angiogenesis | ||||
| Clinical Availability Status | Clinically available (targeted therapy options); ICCA detection rate of 10-15% | ||||
| Notes and Dynamics | |||||
| Biomarker | IDH1/2 (mutation) | Full name | Isocitrate dehydrogenase 1/2 mutations | Molecular Type | Nucleic acid (DNA mutation) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis, prognosis, selection of targeted therapy | ||
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Tissue/plasma/bile (NGS, ddPCR) | ||
| Pathobiological Mechanisms | Mutations lead to the accumulation of 2-hydroxyglutaric acid (2-HG), inhibit cell differentiation, and promote tumorigenesis | ||||
| Clinical Availability Status | Clinically available (targeted therapy option); iCCA is common | ||||
| Notes and Dynamics | |||||
| Biomarker | TP53 (mutation) | Full name | Tumor protein p53 mutations | Molecular Type | Nucleic acid (DNA mutations) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis, prognosis, selection of targeted therapy | ||
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA, eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Tissue/plasma/bile (NGS, Sanger sequencing) | ||
| Pathobiological Mechanisms | Mutations can lead to DNA damage repair defects, genome instability, accelerate tumor progression Mutations lead to the accumulation of 2-hydroxyglutaric acid (2-HG), inhibit cell differentiation, and promote tumorigenesis | ||||
| Clinical Availability Status | Clinical validation; One of the most common mutation types | ||||
| Notes and Dynamics | Detection rate was 38.1%, and the TuBianZhe may be sensitive to PARP inhibitors, HR pathway TuBianZhe survival was significantly shortened | ||||
| Biomarker | KRAS mutations () | Full name | Kirsten rat sarcoma viral oncogene | Molecular Type | Nucleic acid (DNA mutation) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis, prognosis, selection of targeted therapy | ||
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Tissue/plasma/bile (NGS, ddPCR) | ||
| Pathobiological Mechanisms | Mutations such as G12D/V/Q61H activate MAPK pathway and promote tumor proliferation, drug resistance and immunosuppression | ||||
| Clinical Availability Status | Clinical validation/guideline recommendation; The detection rate is high in eCCA | ||||
| Notes and Dynamics | A G12 / G13 mutations suggest poor prognosis shrink (OS), KRAS G12C inhibitors in clinical trials; CtDNA detection sensitivity 80%, specificity of 93% | ||||
| Biomarker | sCD14-ST (presepsin) | Full name | Soluble CD14 subtype | Molecular Type | Protein (soluble CD14 isoform) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Differential diagnosis (infection vs tumor) | ||
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA, eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Serum (immunoassay) | ||
| Pathobiological Mechanisms | Advanced cholangiocarcinoma can be elevated, which is related to tumor-associated phagocytosis; Bacterial infection higher specificity | ||||
| Clinical Availability Status | Research validation; High infection specificity | ||||
| Notes and Dynamics | |||||
| Biomarker | CRP (C-reactive protein) | Full name | C-reactive protein | Molecular Type | Protein |
| Molecular Formula | Molecular Weight | ~115 kDa | Core Functional Dimensions | Inflammation monitoring, prognosis | |
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA, eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Serum (immunoturbidimetry, POCT) | ||
| Pathobiological Mechanisms | Tumor-related inflammatory markers reflect the degree of inflammation in the tumor microenvironment | ||||
| Clinical Availability Status | Commonly used in clinic (inflammation monitoring); nonspecific | ||||
| Notes and Dynamics | Often associated with other markers build diagnostic panel (such as CRP/PIGR/VWF), AUC can reach 0.99, improve specificity | ||||
| Biomarker | Procalcitonin (PCT) | Full name | Procalcitonin | Molecular Type | Protein |
| Molecular Formula | Molecular Weight | ~13 kDa | Core Functional Dimensions | Differential diagnosis (infection vs tumor) | |
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA, eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Serum (immunoassay, POCT) | ||
| Pathobiological Mechanisms | Advanced cholangiocarcinoma can be abnormally elevated, which is related to tumor progression; septic shock-like elevation may also occur in the absence of bacterial infection | ||||
| Clinical Availability Status | Clinically available (infection identification); It should be combined with the clinical scenario | ||||
| Notes and Dynamics | Patients with advanced cholangiocarcinoma may have a high level of >100ng/mL, and bacterial infection should be excluded to avoid misjudgment | ||||
| Biomarker | MUC4/MUC5AC | Full name | Mucin 4 / Mucin 5AC | Molecular Type | Protein (mucin) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis and prognosis | ||
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA, eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | |||
| Pathobiological Mechanisms | The abnormal secretion of tumor cells is involved in tumor adhesion, invasion and immune escape | ||||
| Clinical Availability Status | Study validation; High specificity | ||||
| Notes and Dynamics | |||||
| Biomarker | Osteopontin | Full name | Osteopontin | Molecular Type | Protein (osteopontin) |
| Molecular Formula | Molecular Weight | ~44 kDa | Core Functional Dimensions | Diagnosis and Prognosis | |
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA, eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Serum (ELISA) | ||
| Pathobiological Mechanisms | It is involved in cell adhesion, migration and survival, and promotes tumor progression and metastasis; And regulate the tumor microenvironment | ||||
| Clinical Availability Status | Study validation; And is associated with postoperative survival | ||||
| Notes and Dynamics | Elevated preoperative serum levels indicate poor prognosis and can be used as an indicator of recurrence risk assessment. The serum level in iCCA patients was significantly higher than that in benign biliary diseases | ||||
| Biomarker | MMP-7 | Full name | Matrix metalloproteinase-7 | Molecular Type | Protein (matrix metalloproteinase 7) |
| Molecular Formula | Molecular Weight | ~28 kDa (proenzyme) | Core Functional Dimensions | Diagnosis and Prognosis | |
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA, eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Serum (ELISA) | ||
| Pathobiological Mechanisms | It degrades extracellular matrix and promotes tumor invasion, metastasis, and angiogenesis | ||||
| Clinical Availability Status | Study validation; It can distinguish malignant from benign biliary obstruction | ||||
| Notes and Dynamics | In patients with obstructive jaundice, elevated levels suggest the possibility of iCCA, and preoperative levels are associated with the risk of postoperative recurrence | ||||
| Biomarker | CYFRA 21-1 | Full name | Cytokeratin 19 fragment | Molecular Type | Protein (cytokeratin 19 fragment) |
| Molecular Formula | Protein fragment | Molecular Weight | ~40 kDa | Core Functional Dimensions | Diagnosis and Prognosis |
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA, eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Serum (Immunoassay) | ||
| Pathobiological Mechanisms | Cholangiocarcinoma cells are released after apoptosis, reflecting tumor burden, and the increase is not obvious in benign biliary diseases | ||||
| Clinical Availability Status | Research validation; It is more specific than CA19-9 | ||||
| Notes and Dynamics | |||||