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Biomarker Platelet - Lymphocyte thewire (PLR) Full name Platelet-to-Lymphocyte Ratio Molecular Type Hematology indexes
Molecular Formula Molecular Weight Core Functional Dimensions Prognosis and prediction of immune-related adverse reactions
Disease(or Constitution) Hepatocellular Carcinoma (HCC) Disease Subtypes /
Organ Liver Test Sample / Technology Platform Whole blood (routine blood test)
Pathobiological Mechanisms Reflect inflammatory and blood coagulation state, high PLR suggests tumor progression increased risk
Clinical Availability Status This study verified that PLR>300 was an independent risk factor for irAEs (≥ grade 2)
Notes and Dynamics The combination of PLR and NLR can optimize the prognostic stratification efficiency
Biomarker Neutrophil-Lymphocyte Ratio (NLR) Full name Neutrophil-to-Lymphocyte Ratio Molecular Type Hematological parameters
Molecular Formula Molecular Weight Core Functional Dimensions Prognosis and prediction of treatment response
Disease(or Constitution) Hepatocellular Carcinoma (HCC) - Disease Subtypes /
Organ Liver Test Sample / Technology Platform Whole blood (routine blood test)
Pathobiological Mechanisms Reflect the state of systemic inflammation, high NLR hint immunosuppression microenvironment
Clinical Availability Status Clinically useful (prognostic evaluation) : independent prognostic indicator, negatively correlated with ICIs response
Notes and Dynamics Can be integrated into the HIPI, CRAFITY composite scoring system, etc
Biomarker Microsatellite Instability (MSI) Full name Microsatellite Instability Molecular Type Nucleic acid (DNA)
Molecular Formula Molecular Weight Core Functional Dimensions Predicting response to immunotherapy
Disease(or Constitution) Hepatocellular Carcinoma (HCC) - Disease Subtypes /
Organ Liver Test Sample / Technology Platform Tumor Tissue /ctDNA (NGS)
Pathobiological Mechanisms DNA mismatch repair defects lead to abnormal microsatellite sequences and enhance immunogenicity
Clinical Availability Status The incidence of MSI-H in HCC is low (<5%), and it only has predictive value for some patients
Notes and Dynamics MSI -h HCC patients may benefit from PD - 1 inhibitor treatment
Biomarker Tumor Mutational Burden (TMB) Full name Tumor Mutational Burden Molecular Type Nucleic acid (DNA)
Molecular Formula Molecular Weight Core Functional Dimensions Predicting response to immunotherapy
Disease(or Constitution) Hepatocellular Carcinoma (HCC) - Disease Subtypes /
Organ Liver Test Sample / Technology Platform Tumor tissue/ctDNA (NGS)
Pathobiological Mechanisms The total number of non-synonymous mutations in the tumor genome, high TMB can produce more neoantigens
Clinical Availability Status Study validation: The incidence of high TMB in HCC is low, and its value as a predictor alone is limited
Notes and Dynamics The combination of TMB and TILs can improve the accuracy of ICIs efficacy prediction
Biomarker PD-L1 Full name Programmed death-ligand 1 Molecular Type Protein
Molecular Formula Molecular Weight Core Functional Dimensions To predict immunotherapy response and prognosis
Disease(or Constitution) Hepatocellular Carcinoma (HCC) - Disease Subtypes /
Organ Liver Test Sample / Technology Platform Tumor tissue /CTCs (IHC, flow cytometry)
Pathobiological Mechanisms Tumor cell surface molecules, combined with PD-1, inhibit T cell activation and mediate immune escape
Clinical Availability Status Study validation: The correlation between PD-L1 expression in tumor tissue and the efficacy of ICIs is not clear
Notes and Dynamics PD-L1+CTCs can more dynamically reflect the response to immunotherapy and is a potential predictor
Biomarker Outside the secrete body related markers (EV - derived GPC3, AFP mRNA, miR - 21-5 p) Full name Extracellular vesicle (Exosome)-derived markers (e.g., GPC3 protein/mRNA, AFP mRNA, miR-21-5p) Molecular Type Cell derivatives (containing protein /RNA)
Molecular Formula Molecular Weight Core Functional Dimensions Diagnosis, prognosis, and monitoring
Disease(or Constitution) Hepatocellular Carcinoma (HCC) - Disease Subtypes /
Organ Liver Test Sample / Technology Platform Serum/plasma lactate (overspeed centrifugal + ELISA/qRT - PCR)
Pathobiological Mechanisms Exosomes released by tumor cells carry tumor-specific molecules and mediate intercellular communication
Clinical Availability Status This study verified that the diagnostic efficiency of exosomal GPC3 was better than that of serum GPC3
Notes and Dynamics Exosomal proteins such as CCT8 and CFL1 are related to vascular invasion and can be used for prognostic stratification
Biomarker MALAT1, LINC00152, Linc00974 etc Full name Long non-coding RNAs (e.g., MALAT1, LINC00152, Linc00974) Molecular Type Nucleic acids (RNA, long non-coding RNA)
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/tumor tissue (qRT - PCR, RNA - seq)
Pathobiological Mechanisms Control the miRNA expression or chromatin reconstruction, promote EMT and tumor metastasis
Clinical Availability Status Cutting-edge research: serum LINC00152 can distinguish between HCC and liver cirrhosis
Notes and Dynamics Combined with AFP, LINC00152 can improve the diagnostic specificity and is expected to be included in the composite marker panel
Biomarker miR-9, miR-17-5p, miR-21, miR-1246, etc. (Circular) Full name Circular and other microRNAs Molecular Type Nucleic acid (RNA)
Molecular Formula Molecular Weight Core Functional Dimensions Prognosis, Surveillance
Disease(or Constitution) Hepatocellular Carcinoma (HCC) Disease Subtypes /
Organ Liver Test Sample / Technology Platform Serum/plasma/plasma exosomes (qRT-PCR, digital PCR)
Pathobiological Mechanisms Circulating mirnas have high stability, and their expression changes reflect tumor progression and treatment response
Clinical Availability Status Validation: multiple studies confirm related to OS, DFS
Notes and Dynamics Secrete body outside the miRNA detection sensitivity is better than that of free micrornas, is a hot spot in the liquid biopsy
Biomarker MiR - 21, miR - 122, miR - 192, miR - 26 a, a miR - 29 (including organization/circular) Full name MicroRNAs (e.g., miR-21, miR-122, miR-192, miR-26a, miR-29) Molecular Type Nucleic acid (RNA)
Molecular Formula Molecular Weight Core Functional Dimensions Diagnosis, prognosis, predict treatment response
Disease(or Constitution) Hepatocellular Carcinoma (HCC) - Disease Subtypes /
Organ Liver Test Sample / Technology Platform Serum/plasma/tumor tissue (qRT-PCR, NGS)
Pathobiological Mechanisms It regulates the expression of oncogenes/tumor suppressor genes and participates in tumor proliferation, invasion and drug resistance
Clinical Availability Status Research validation: many micrornas panel in the diagnosis of early HCC AUC 0.824 to 0.977
Notes and Dynamics miR-21 was associated with sorafenib resistance, and miR-1246 could predict early recurrence after surgery
Biomarker Cell-free DNA (cfDNA) Full name Cell-free DNA Molecular Type Nucleic acid (DNA)
Molecular Formula Molecular Weight Core Functional Dimensions Diagnosis, prognosis, and monitoring
Disease(or Constitution) Hepatocellular Carcinoma (HCC) - Disease Subtypes /
Organ Liver Test Sample / Technology Platform Plasma (NGS, NEEM-seq)
Pathobiological Mechanisms There are differences in the characteristics of circulating cell-free DNA between HCC patients and healthy people, reflecting tumor burden
Clinical Availability Status Research validation: age, AFP building model, specificity of 100%
Notes and Dynamics The combined detection of 5hmC and 5mC can improve the accuracy of recurrence prediction
Biomarker Circulating Tumor DNA (ctDNA) Full name Circulating Tumor DNA Molecular Type Nucleic acid (DNA)
Molecular Formula Molecular Weight Core Functional Dimensions Diagnosis, prognosis and monitoring treatment response
Disease(or Constitution) Hepatocellular Carcinoma (HCC) Disease Subtypes /
Organ Liver Test Sample / Technology Platform Plasma (NGS, digital PCR, methylation sequencing)
Pathobiological Mechanisms Mutated DNA fragments released by apoptosis/necrosis of tumor cells reflect the mutation spectrum of tumor genes
Clinical Availability Status TERT, TP53, CTNNB1 and other mutations could be detected
Notes and Dynamics Methylation ctDNA markers (such as DBX2, TGR5) in early diagnosis of the sensitivity of 87%, is expected to be in clinical
Biomarker Circulating Tumor Cells (CTCs) Full name Circulating Tumor Cells Molecular Type Cells
Molecular Formula Molecular Weight Core Functional Dimensions
Disease(or Constitution) Hepatocellular Carcinoma (HCC) Disease Subtypes Peripheral blood (flow cytometry, microfluidic chip, CellSearch platform)
Organ Liver Test Sample / Technology Platform As "seed" of metastasis, through EMT adapt to the environment, promote the distant metastasis
Pathobiological Mechanisms Diagnosis, prognosis, monitoring, and prediction of treatment response
Clinical Availability Status Research validation/clinical monitoring tool: EpCAM+CTCs≥2 indicates an increased risk of postoperative recurrence
Notes and Dynamics Combined detection of mRNA can improve the sensitivity, and PD-L1+CTCs are associated with the efficacy of immunotherapy
Biomarker GALAD model (age + sex +AFP+AFP-L3+DCP) Full name Gender, Age, AFP-L3, AFP, DCP Molecular Type Composite index (protein + clinical parameters)
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+ algorithm analysis)
Pathobiological Mechanisms To improve the specificity and sensitivity of HCC diagnosis by integrating multi-dimensional parameters
Clinical Availability Status In clinical practice, clinical validation: better than single marker, for early HCC detection efficiency
Notes and Dynamics Multi-center clinical validation is underway, and it is expected to become a standardized screening tool
Biomarker Midkine (MDK) Full name Midkine Molecular Type Protein
Molecular Formula Molecular Weight Core Functional Dimensions Diagnosis, Prognosis
Disease(or Constitution) Hepatocellular Carcinoma (HCC) Disease Subtypes /
Organ Hepatocellular Carcinoma (HCC) Test Sample / Technology Platform Serum (ELISA)
Pathobiological Mechanisms Heparin combined with growth factors, promote cell proliferation and metastasis of liver cancer
Clinical Availability Status The validation: high sensitivity for AFP negative HCC diagnosis
Notes and Dynamics It shows potential in differentiating early-stage HCC from cirrhosis
Biomarker Osteopontin (SPP1) Full name Secreted phosphoprotein 1 (Osteopontin) 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)
Pathobiological Mechanisms Tumor microenvironment secreted protein, and promote the tumor invasion and angiogenesis
Clinical Availability Status Study validation: the expression was increased in early HCC and correlated with recurrence
Notes and Dynamics It can be used as an auxiliary indicator for prognostic risk stratification
Biomarker Golgi protein 73 (GP73) Full name Golgi protein 73 / Golgi membrane protein 1 (GOLM1) 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 Serum/tumor tissue (ELISA, IHC)
Pathobiological Mechanisms Golgi protein, increased liver cancer cells, involved in tumor progression
Clinical Availability Status It has complementary diagnostic value for AFP-negative HCC
Notes and Dynamics EV-derived GP73 mRNA can be used for therapeutic monitoring

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This study was supported by the Scientific Research Innovation Capability Support Project for Young Faculty (SRICSPYF-ZY2025112), the Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China (JYB2025XDXM612)

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