| Biomarker | Cyclase - associated protein 2 (CAP2) | Full name | Cyclase-associated protein 2 | Molecular Type | protein |
| Molecular Formula | diagnosis | Molecular Weight | Core Functional Dimensions | ||
| Disease(or Constitution) | Hepatocellular Carcinoma (HCC) | Disease Subtypes | / | ||
| Organ | Liver | Test Sample / Technology Platform | Tumor tissue/serum (IHC, ELISA) | ||
| Pathobiological Mechanisms | It can regulate cytoskeleton remodeling and promote the migration and invasion of hepatocellular carcinoma cells | ||||
| Clinical Availability Status | Cutting-edge research: in HCC high expression, associated with metastasis potential | ||||
| Notes and Dynamics | Large-scale clinical data are lacking, and further verification is needed | ||||
| Biomarker | Glutamine synthetase (GS) | Full name | Glutamine synthetase | Molecular Type | Protein |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | diagnosis | ||
| Disease(or Constitution) | Hepatocellular Carcinoma (HCC) - | Disease Subtypes | / | ||
| Organ | Liver | Test Sample / Technology Platform | Tumor tissue (IHC) | ||
| Pathobiological Mechanisms | Abnormal activation in liver cancer cells and participate in glutamine metabolism support tumor growth | ||||
| Clinical Availability Status | Study validation: Used for pathological differential diagnosis | ||||
| Notes and Dynamics | With GPC3 joint detection can improve the rate of early HCC diagnosis | ||||
| Biomarker | Heat shock protein 70 (HSP70) | Full name | Heat shock protein 70 | Molecular Type | Proteins |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis, Prognosis | ||
| Disease(or Constitution) | Hepatocellular Carcinoma (HCC) - | Disease Subtypes | / | ||
| Organ | Liver | Test Sample / Technology Platform | Tumor tissue/serum (IHC, Western blot) | ||
| Pathobiological Mechanisms | Tumor cell stress response protein, inhibits apoptosis and promotes angiogenesis | ||||
| Clinical Availability Status | It was highly expressed in HCC tissues and correlated with poor prognosis | ||||
| Notes and Dynamics | It has not been clinically validated, and larger cohort studies are needed | ||||
| Biomarker | Glypican - 3 (GPC3) | Full name | Glypican-3 | Molecular Type | Protein |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis, Prognosis | ||
| Disease(or Constitution) | Hepatocellular Carcinoma (HCC) - | Disease Subtypes | / | ||
| Organ | Liver | Test Sample / Technology Platform | Tumor tissue/serum (IHC, ELISA) | ||
| Pathobiological Mechanisms | Liver cancer cell surface glycoprotein, activate the Wnt signaling pathway to promote proliferation | ||||
| Clinical Availability Status | Research validation: IHC is used for pathological diagnosis, and serum detection is in the clinical trial stage | ||||
| Notes and Dynamics | EV-derived GPC3 mRNA is a potential marker for early detection | ||||
| Biomarker | Des - gamma carboxy prothrombin (DCP)/PIVKA - II) | Full name | Des-γ-carboxy prothrombin / Protein induced by vitamin K absence or antagonist-II | Molecular Type | protein |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis, Prognosis | ||
| Disease(or Constitution) | Hepatocellular Carcinoma (HCC) | Disease Subtypes | / | ||
| Organ | Liver | Test Sample / Technology Platform | Serum (ELISA, RIA) | ||
| Pathobiological Mechanisms | Abnormal prothrombin caused by vitamin K deficiency in hepatocellular carcinoma cells promotes tumor invasion | ||||
| Clinical Availability Status | Clinically available (auxiliary diagnosis) : Combination with AFP can improve diagnostic accuracy | ||||
| Notes and Dynamics | AAP grading components, the inhibitor used in PD - 1 curative effect prediction | ||||
| Biomarker | AFP-L3 | Full name | Lectin-reactive alpha-fetoprotein fraction (Lens culinaris agglutinin-reactive AFP) | Molecular Type | Protein |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis and Prognosis | ||
| Disease(or Constitution) | Hepatocellular Carcinoma (HCC) - | Disease Subtypes | / | ||
| Organ | Liver | Test Sample / Technology Platform | Serum (affinity electrophoresis, ELISA) | ||
| Pathobiological Mechanisms | AFP different plasmids, associated with malignant degree of liver cancer cells | ||||
| Clinical Availability Status | Clinical validation: used for additional diagnosis of HCC with negative AFP or low levels | ||||
| Notes and Dynamics | The core components of GALAD model can improve the diagnostic specificity of early HCC | ||||
| Biomarker | Alpha-fetoprotein (AFP) | Full name | Alpha-fetoprotein | Molecular Type | Protein |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis, prognosis, and prediction of treatment response | ||
| Disease(or Constitution) | Hepatocellular Carcinoma (HCC) - | Disease Subtypes | / | ||
| Organ | Liver | Test Sample / Technology Platform | Serum/plasma (ELISA, RIA) | ||
| Pathobiological Mechanisms | Embryonic proteins abnormally expressed by hepatocellular carcinoma cells are involved in tumor proliferation and immunosuppression | ||||
| Clinical Availability Status | Clinically available (routine screening) : the sensitivity of single detection is 47-64%, and can be increased to 63% when combined with ultrasound | ||||
| Notes and Dynamics | The traditional core marker AFP≥400 ng/mL can predict the benefit of ramucirumab treatment. A decrease of >20% at 2-8 weeks after treatment indicated a good response | ||||
| Biomarker | acetone | Full name | acetone | Molecular Type | Metabolites |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis and Prognosis | ||
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Duodenal fluid (gas chromatography - mass spectrometry) | ||
| Pathobiological Mechanisms | Tumor abnormal energy metabolism product, reflecting the tumor metabolic activity | ||||
| Clinical Availability Status | The validation; Predicting malignancy risk | ||||
| Notes and Dynamics | Duodenal fluid levels of acetone in the AUC 0.733, can assist to identify benign and malignant biliary pancreatic lesions | ||||
| Biomarker | Lipid metabolites (SM/PC/Cer) | Full name | Sphingomyelin / Phosphatidylcholine / Ceramide | Molecular Type | Metabolites (sphingomyelin, phosphatidylcholine, ceramide) |
| Molecular Formula | Diagnosis, differential diagnosis | Molecular Weight | Core Functional Dimensions | ||
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA (IDH1/2 mutated) | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Serum (liquid chromatography - mass spectrometry) | ||
| Pathobiological Mechanisms | Lipid metabolic abnormalities, tumor cells were tumor metabolic phenotype | ||||
| Clinical Availability Status | Study validation; Identify iCCA and HCC effectiveness is good | ||||
| Notes and Dynamics | 43:2 (SM), PC (O - 16-0 / plot) composed of panel, identify iCCA and HCC AUC > 0.90, is better than that of CA19-9 and AFP | ||||
| Biomarker | 2-Hydroxyglutaric acid (2-HG) | Full name | D-2-hydroxyglutaric acid | Molecular Type | metabolites |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis and targeted therapy monitoring | ||
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA, eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Serum (liquid chromatography - mass spectrometry) | ||
| Pathobiological Mechanisms | Characteristic metabolites of IDH1/2 mutated tumors, which promote tumorigenesis and progression | ||||
| Clinical Availability Status | Clinical validation; Patient-specific markers for IDH mutations | ||||
| Notes and Dynamics | Levels associated with the tumor load, can be real-time monitoring ivosidenib treatment response; Diagnosis of IDH mutation CCA sensitivity 83%, specificity of 90% | ||||
| Biomarker | CTCs (circulating tumor cells) | Full name | Circulating tumor cells | Molecular Type | cells |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Prognosis, metastasis, MRD monitoring | ||
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA, eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Whole blood (CellSearch, microfluidic technology) | ||
| Pathobiological Mechanisms | Tumor cells fall off into the bloodstream, transfer of precursor, reflect the tumor invasion ability | ||||
| Clinical Availability Status | The validation; The detection sensitivity needs to be improved | ||||
| Notes and Dynamics | CTCs ≥2 indicates poor prognosis. Joint ctDNA detection can increase the efficiency of the MRD monitoring (AUC) 0.92, is better than that of CA19-9 | ||||
| Biomarker | MiR - 200 family | Full name | microRNA-200 family (e.g., miR-200a/b/c) | Molecular Type | Nucleic acid (miRNA) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis, prognosis and monitoring | ||
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Serum/bile (qRT-PCR) | ||
| Pathobiological Mechanisms | Inhibition of EMT (targeting ZEB1/ZEB2) reduces tumor metastasis | ||||
| Clinical Availability Status | The validation; ECCA low expression suggests high shifting risk | ||||
| Notes and Dynamics | |||||
| Biomarker | miR-34a | Full name | microRNA-34a | Molecular Type | Nucleic acid (miRNA) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis, prognosis and therapeutic targets | ||
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA, eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Serum/plasma (qRT PCR and NGS) | ||
| Pathobiological Mechanisms | Targeted Notch, the Bcl - 2, inhibition of tumor proliferation and induce apoptosis | ||||
| Clinical Availability Status | Developing clinical validation (therapy); Tumor suppressor mirnas | ||||
| Notes and Dynamics | Mimic (MRX34) in clinical trials, used to restore tumor suppressor function; Low expression of MRX34 is associated with tumor progression | ||||
| Biomarker | miR-221/222 | Full name | microRNA-221/222 | Molecular Type | Nucleic acid (miRNA) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis and prognosis | ||
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Serum/bile (qRT - PCR) | ||
| Pathobiological Mechanisms | Targeted p27, PTEN, promote cell cycle progression and apoptosis resistance | ||||
| Clinical Availability Status | Study validation; It was highly expressed in iCCA | ||||
| Notes and Dynamics | High expression of ICCA indicates strong invasion and is associated with poor prognosis. Inhibition of the expression can reduce the tumor proliferation activity | ||||
| Biomarker | miR-155 | Full name | microRNA-155 | Molecular Type | Nucleic acid (miRNA) |
| 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 | Serum/bile (qRT - PCR) | ||
| Pathobiological Mechanisms | Activation of inflammation (STAT3), promote the tumor invasion and immunosuppression | ||||
| Clinical Availability Status | The validation; And associated with inflammation-related tumors | ||||
| Notes and Dynamics | |||||
| Biomarker | miR-21 | Full name | microRNA-21 | Molecular Type | Nucleic acid (miRNA) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis, prognosis and drug resistance monitoring | ||
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA, eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | / plasma/serum bile (qRT PCR and NGS) | ||
| Pathobiological Mechanisms | Targeting PTEN, PDCD4, promote tumor proliferation, invasion, and gemcitabine/cisplatin resistance | ||||
| Clinical Availability Status | The validation; High expression suggests poor prognosis | ||||
| Notes and Dynamics | Associated with EMT, restrain can be enhanced after chemotherapy sensitivity; Serum/high expression of bile, can be used as a noninvasive diagnostic markers | ||||