| Biomarker | E-cadherin (epithelial calcium adhesion protein) | Full name | Epithelial cadherin (CDH1) | Molecular Type | Protein/nucleic acid (DNA) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis and prognosis | ||
| Disease(or Constitution) | Gastric Cancer | Disease Subtypes | Diffuse type gastric cancer | ||
| Organ | Stomach | Test Sample / Technology Platform | Tumor tissues (IHC, NGS) | ||
| Pathobiological Mechanisms | CDH1 gene is a cell adhesion molecule encoded by CDH1 gene. The mutation or methylation of CDH1 gene is common in diffuse type of gastric cancer, which leads to the loss of E-cadherin expression and the decrease of intercellular adhesion, promotes the diffuse invasion of tumor cells and peritoneal metastasis, and is related to the typical pathological characteristics of diffuse type of gastric cancer | ||||
| Clinical Availability Status | Clinical usefulness (subtype diagnosis) : for the diagnosis and classification of diffuse gastric cancer (especially hereditary diffuse gastric cancer), CDH1 mutation carriers should be screened regularly | ||||
| Notes and Dynamics | CDH1 germline mutation, a characteristic marker of diffuse gastric cancer, is the cause of hereditary diffuse gastric cancer (HDGC). Prophylactic gastrectomy is recommended for carriers. Patients with E-cadherin deletion have a high risk of peritoneal metastasis, and surveillance for peritoneal metastasis should be strengthened | ||||
| Biomarker | APC (Adenomatous polyposis coli) | Full name | Adenomatous polyposis coli protein | Molecular Type | Protein/nucleic acid (DNA) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis and prognosis | ||
| Disease(or Constitution) | Gastric Cancer | Disease Subtypes | Intestinal type gastric cancer | ||
| Organ | Stomach | Test Sample / Technology Platform | Tumor tissues (IHC, methylation-PCR, NGS) | ||
| Pathobiological Mechanisms | APC gene methylation or mutation is common in intestinal type gastric cancer, which can not inhibit β-catenin nuclear translocation, activate Wnt pathway, promote abnormal cell proliferation, intestinal metaplasia and tumorigenesis, and is positively correlated with the progression of gastric precancerous lesions | ||||
| Clinical Availability Status | Basic research/early clinical: used for monitoring the progression of gastric precancerous lesions (such as adenoma), auxiliary diagnosis of intestinal type gastric cancer, needs clinical verification | ||||
| Notes and Dynamics | As a key marker for the occurrence and development of intestinal type gastric cancer, APC methylation detection can be used for the screening of high-risk population of intestinal type gastric cancer, and combined detection with serum PG can improve the detection rate of gastric precancerous lesions, which is an important indicator for the primary prevention and early intervention of intestinal type gastric cancer | ||||
| Biomarker | TP53 (tumor protein p53) | Full name | Tumor protein p53 | Molecular Type | Protein/nucleic acid (DNA) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis, prognosis, prediction | ||
| Disease(or Constitution) | Gastric Cancer | Disease Subtypes | Intestinal-type gastric cancer/diffuse gastric cancer | ||
| Organ | Stomach | Test Sample / Technology Platform | Tumor tissue (IHC, NGS), circulating tumor DNA (ctDNA, NGS) | ||
| Pathobiological Mechanisms | TP53 is a tumor suppressor gene, which is mutated in about 50% of gastric cancer. Mutant p53 loses its function of DNA damage repair and cell cycle regulation, and promotes tumor proliferation, invasion and chemotherapy resistance | ||||
| Clinical Availability Status | Clinical research stage: it is used for molecular typing and prognosis of gastric cancer, and some studies are used for chemotherapy efficacy prediction, but not as a routine test | ||||
| Notes and Dynamics | Patients with TP53 mutation, the most common gene mutation marker of gastric cancer, have poor response to platinum-based chemotherapy, and combined with radiotherapy can improve the efficacy. Dynamic monitoring of TP53 mutation by ctDNA can detect early recurrence, which is the core index for the study of molecular mechanism and individualized treatment of gastric cancer | ||||
| Biomarker | Fusobacterium nucleatum | Full name | Fusobacterium nucleatum | Molecular Type | Pathogens (bacteria) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Pathogens (bacteria) | ||
| Disease(or Constitution) | Gastric Cancer | Disease Subtypes | Intestinal-type gastric cancer/diffuse gastric cancer | ||
| Organ | Stomach | Test Sample / Technology Platform | Tumor tissue (16S rRNA sequencing, qPCR), saliva (qPCR) | ||
| Pathobiological Mechanisms | F. nucleatum is enriched in gastric cancer tissues, which promotes inflammation and inhibits T cell function by activating TLR4/NF-κB pathway, and is positively correlated with gastric cancer progression and chemotherapy resistance. Patients with high abundance of F. nucleatum have poor prognosis | ||||
| Clinical Availability Status | Basic research/early clinical: small sample studies have confirmed its prognostic value, which is related to the immunosuppressive microenvironment, and large-scale clinical validation is needed | ||||
| Notes and Dynamics | As a representative of gut/oral microbiota markers, saliva detection is convenient and minimally invasive, and can be used as an auxiliary indicator for the prognosis and immunotherapy response of gastric cancer. F. nucleatum targeted antibiotics (such as metronidazole) combined with immunotherapy may enhance the efficacy | ||||
| Biomarker | Helicobacter pylori (H. pylori) | Full name | Helicobacter pylori | Molecular Type | Pathogens (bacteria) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Susceptibility, early diagnosis | ||
| Disease(or Constitution) | Gastric Cancer | Disease Subtypes | Intestinal-type/diffuse type gastric cancer | ||
| Organ | Stomach | Test Sample / Technology Platform | Gastric mucosa tissues (pathological staining, PCR), serum (H. pylori antibody detection), feces (antigen detection) | ||
| Pathobiological Mechanisms | Class I carcinogens, about 70%-90% of gastric cancer are related to H. pylori infection. Virulence factors such as CagA and VacA induce chronic inflammation, gastric mucosal atrophy, intestinal metaplasia, and finally develop into gastric cancer by activating the NF-κB and Wnt pathways | ||||
| Clinical Availability Status | Clinical use (risk assessment/prevention) : it can be used for the screening of high-risk population of gastric cancer. Eradication therapy in H. pylori positive patients can reduce the risk of gastric cancer | ||||
| Notes and Dynamics | As a key marker for primary prevention of gastric cancer, the risk of gastric cancer in patients infected with CagA positive strains is significantly increased. Eradication therapy can reduce the risk of gastric cancer by 30%-40%. Combined detection of serum PG and G-17 can improve the accuracy of screening gastric precancerous lesions | ||||
| Biomarker | piR-823 (PIWI interacting RNA-823) | Full name | PIWI-interacting RNA-823 | Molecular Type | Non-coding RNA (piRNA) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis and Prognosis | ||
| Disease(or Constitution) | Gastric Cancer | Disease Subtypes | Intestinal-type gastric cancer/diffuse gastric cancer | ||
| Organ | Stomach | Test Sample / Technology Platform | Serum (qPCR, digital PCR), tumor tissue (qPCR) | ||
| Pathobiological Mechanisms | piRNA, the low expression of piR-823 in gastric cancer tissues and serum, inhibits tumor cell proliferation by regulating DNA methylation (such as inhibiting c-MYC promoter methylation), and low expression is positively correlated with tumor stage and distant metastasis | ||||
| Clinical Availability Status | Basic research: in the stage of cell experiments and small clinical samples, the mechanism and clinical value need to be further verified | ||||
| Notes and Dynamics | piRNA has been rarely studied in gastric cancer, but its high stability (especially in serum) makes it have potential diagnostic advantages. The combined detection of PIRNA and piR-823 can improve the diagnostic accuracy, which is a new direction for the research of non-coding RNA markers in gastric cancer | ||||
| Biomarker | lncRNA HOTAIR (long non-coding RNA HOTAIR) | Full name | Long non-coding RNA HOX transcript antisense RNA | Molecular Type | Non-coding RNA (lncRNA) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Prognosis and Prediction | ||
| Disease(or Constitution) | Gastric Cancer | Disease Subtypes | Intestinal-type/diffuse-type gastric cancer | ||
| Organ | Stomach | Test Sample / Technology Platform | Tumor tissue (qPCR, RNA in situ hybridization), serum (qPCR) | ||
| Pathobiological Mechanisms | Carcinogenic lncRNA, HOTAIR is highly expressed in gastric cancer tissues, which can inhibit the expression of tumor suppressor genes (such as p21) by recruiting PRC2 complex, promote tumor proliferation, invasion and chemotherapy resistance (such as resistance to cisplatin), and patients with high expression have poor response to chemotherapy | ||||
| Clinical Availability Status | Basic research/early clinical: Small sample clinical studies have shown its prognostic value and positive correlation with the risk of gastric cancer recurrence, which needs large-scale validation | ||||
| Notes and Dynamics | Representative markers in the field of lncRNA can be used as predictors of the prognosis and chemotherapy resistance of gastric cancer. siRNA or antisense oligonucleotide (ASO) targeting HOTAIR can reverse chemotherapy resistance, which is a potential strategy for combined chemotherapy | ||||
| Biomarker | hsa_circ_0001789 (circular RNA) | Full name | Circular RNA hsa_circ_0001789 | Molecular Type | Non-coding RNA (circRNA) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis and Prognosis | ||
| Disease(or Constitution) | Gastric Cancer | Disease Subtypes | Intestinal-type/diffuse-type gastric cancer | ||
| Organ | Stomach | Test Sample / Technology Platform | Plasma (qPCR, digital PCR), tumor tissue (qPCR, in situ hybridization) | ||
| Pathobiological Mechanisms | The low expression of hsa_circ_0001789 in gastric cancer tissues and plasma can regulate the downstream FOXO3a pathway by sponge adsorption of miR-182-5p, and inhibit the proliferation and invasion of tumor cells. The low expression is positively correlated with late tumor stage and lymph node metastasis | ||||
| Clinical Availability Status | Basic research: it is in the stage of cell and animal experiments, and clinical samples are less verified | ||||
| Notes and Dynamics | circRNA has high stability (resistance to nuclease degradation) and is an ideal liquid biopsy marker. hsa_circ_0001789 has good stability in plasma. Large-scale clinical studies are needed to verify its diagnostic and prognostic value in the future | ||||
| Biomarker | miR-375 (microrNA-375) | Full name | microRNA-375 | Molecular Type | Non-coding RNA (microRNA) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis and prognosis | ||
| Disease(or Constitution) | Gastric Cancer | Disease Subtypes | Intestinal-type gastric cancer/diffuse gastric cancer | ||
| Organ | Stomach | Test Sample / Technology Platform | Serum (qPCR, digital PCR), tumor tissue (qPCR, in situ hybridization) | ||
| Pathobiological Mechanisms | As a tumor suppressor microRNA, the expression of miR-375 in gastric cancer tissues and serum is low, which inhibits tumor cell proliferation and induces apoptosis by targeting oncogenes such as YAP1 and AEG-1. Patients with low expression of Mir-375 have strong tumor invasion and short survival time | ||||
| Clinical Availability Status | Basic research/early clinical: the diagnostic sensitivity is about 70%, the specificity is about 85%, and it is in the clinical verification stage of small samples | ||||
| Notes and Dynamics | Serum miR-375 level is correlated with the degree of gastric mucosal atrophy and intestinal metaplasia, which can be used as a monitoring indicator for the progression of gastric precancerous lesions. Combined with gastroscopy, the detection rate of early gastric cancer can be improved | ||||
| Biomarker | miR-21 (microrNA-21) | Full name | microRNA-21 | Molecular Type | Non-coding RNA (microRNA) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis, prognosis and prediction | ||
| Disease(or Constitution) | Gastric Cancer | Disease Subtypes | Stomach | ||
| Organ | Test Sample / Technology Platform | Serum (qPCR, digital PCR), tumor tissue (qPCR, in situ hybridization) | |||
| Pathobiological Mechanisms | Carcinogenic microRNA, miR-21 is highly expressed in gastric cancer tissues and serum, which can promote tumor proliferation, invasion and chemotherapy resistance by targeting tumor suppressor genes such as PTEN and PDCD4 and activating PI3K/Akt pathway. Patients with high expression of Mir-21 have poor prognosis | ||||
| Clinical Availability Status | Basic research/early clinical: a large number of basic studies have confirmed its diagnostic and prognostic value, and clinical validation in small samples shows that the diagnostic sensitivity is about 75%, which needs large-scale validation | ||||
| Notes and Dynamics | As a potential non-invasive marker for early diagnosis of gastric cancer, serum miR-21 detection is convenient and minimally invasive, and can be used for high-risk population screening. Combined with other mirnas (such as miR-375 and miR-148a), the diagnostic accuracy can be improved. Antisense oligonucleotide (ASO) targeting miR-21 is a potential therapeutic strategy | ||||
| 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 | ||
| Disease(or Constitution) | Gastric Cancer | Disease Subtypes | Intestinal-type gastric cancer/diffuse gastric cancer | ||
| Organ | Stomach | Test Sample / Technology Platform | Peripheral blood (NGS, digital PCR) | ||
| Pathobiological Mechanisms | DNA fragments released into peripheral blood by apoptosis/necrosis of tumor cells carrying tumor-specific mutations (such as TP53, KRAS, PIK3CA) can be used for early diagnosis of gastric cancer, dynamic monitoring of tumor load, prediction of recurrence and drug resistance | ||||
| Clinical Availability Status | Clinical research stage: early diagnosis and minimal residual disease (MRD) monitoring are in phase II/III clinical practice, and some are used for drug resistance detection of advanced gastric cancer | ||||
| Notes and Dynamics | The "gold standard" of liquid biopsy, MRD monitoring can detect minimal residual disease early after surgery (3-6 months earlier than imaging), dynamic monitoring of ctDNA mutations (such as TP53 and PIK3CA) can guide the adjustment of treatment plan, and standardized detection procedures (such as detection Panel and minimum detection limit) are the key to clinical transformation | ||||
| Biomarker | Circulating tumor cells (CTCS) | Full name | Circulating Tumor Cells | Molecular Type | Cells |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Prognosis, Monitoring | ||
| Disease(or Constitution) | Gastric Cancer | Disease Subtypes | Intestinal-type gastric cancer/diffuse type gastric cancer | ||
| Organ | Stomach | Test Sample / Technology Platform | Peripheral blood (immunomagnetic cell sorting, microfluidic chip, flow cytometry) | ||
| Pathobiological Mechanisms | Tumor cells shed from the primary tumor into the peripheral blood carry the molecular characteristics of the primary tumor. The number of CTCS and epithelial-mesenchymal transition (EMT) phenotype are positively correlated with the stage and metastasis risk of gastric cancer, and can dynamically reflect the treatment response and recurrence | ||||
| Clinical Availability Status | Clinical research stage: Most of them are used for clinical research (such as efficacy monitoring and early warning of recurrence), and some centers are used for prognosis evaluation of advanced gastric cancer | ||||
| Notes and Dynamics | The core indicators of liquid biopsy can realize "real-time biopsy", and dynamic monitoring of the number and molecular characteristics of CTC (such as HER2 and PD-L1) can early detect treatment resistance and recurrence. CTC culture combined with drug sensitivity testing is the future direction of individualized treatment | ||||
| Biomarker | Claudin18.2 (tight junction protein 18.2) | Full name | Claudin-18 splice variant 2 | Molecular Type | Proteins |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis, Prediction | ||
| Disease(or Constitution) | Gastric Cancer | Disease Subtypes | Intestinal-type gastric cancer/diffuse gastric cancer | ||
| Organ | Stomach | Test Sample / Technology Platform | Tumor tissue (IHC), Circulating tumor cells (CTC, flow cytometry) | ||
| Pathobiological Mechanisms | Claudin18.2 protein is normally expressed in differentiated gastric mucosal epithelial cells, and about 30%-40% of gastric cancers have claudin18.2 protein overexpression, which promotes tumor invasion by maintaining tight junctions between tumor cells. Claudin18.2 is the target of CAR-T cell therapy and antibody drug conjugate (ADC) | ||||
| Clinical Availability Status | Clinical research stage: Claudin18.2 CAR-T (such as CT041) is in phase II clinical practice, and ADC drugs are in phase I clinical practice | ||||
| Notes and Dynamics | The popular marker of new targeted therapy for gastric cancer has high safety and limited expression in normal tissues (only gastric mucosa). It has a significant effect on patients with diffuse gastric cancer and peritoneal metastasis. Combined immunotherapy can enhance the anti-tumor effect, which is a new hope for the refractory population of advanced gastric cancer | ||||
| Biomarker | c-MET (mesenchymal-epithelial transforming factor) | Full name | MET proto-oncogene, receptor tyrosine kinase | Molecular Type | Protein/nucleic acid (DNA/RNA) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Prognosis, Prediction | ||
| Disease(or Constitution) | Gastric Cancer | Disease Subtypes | Intestinal-type gastric cancer/diffuse gastric cancer | ||
| Organ | Stomach | Test Sample / Technology Platform | Tumor tissues (IHC, FISH, NGS), circulating tumor DNA (ctDNA, NGS) | ||
| Pathobiological Mechanisms | About 5%-10% gastric cancer has MET gene amplification or protein overexpression, which promotes tumor proliferation, invasion and metastasis by activating HGF/c-MET pathway. It is an important mechanism of chemotherapy resistance and HER2-targeted therapy resistance in gastric cancer | ||||
| Clinical Availability Status | Clinical research stage: it is in phase II clinical verification (such as MET inhibitors combined with chemotherapy) and is not used as a routine test | ||||
| Notes and Dynamics | It is a potential biomarker for targeted therapy of gastric cancer, especially for patients with HER2 targeted resistance caused by MET amplification. Combined with MET inhibitors can reverse drug resistance. Dynamic monitoring of MET amplification by ctDNA can detect drug resistance at an early stage, which is a key target to overcome drug resistance in gastric cancer | ||||
| Biomarker | VEGF/VEGFR2 (vascular endothelial growth factor/receptor 2) | Full name | Vascular endothelial growth factor A / Vascular endothelial growth factor receptor 2 | Molecular Type | Protein/nucleic acid (RNA) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Prognosis, Prediction | ||
| Disease(or Constitution) | Gastric Cancer | Disease Subtypes | Intestinal-type gastric cancer/diffuse gastric cancer | ||
| Organ | Stomach | Test Sample / Technology Platform | Serum (VEGF: ELISA), tumor tissue (VEGFR2: IHC, NGS) | ||
| Pathobiological Mechanisms | VEGF is a key pro-angiogenic factor. Gastric cancer cells highly secrete VEGF and VEGFR2, which activates the downstream PI3K/Akt pathway to promote tumor angiogenesis and provide nutrition for tumor growth. Patients with high expression of VEGFR2 respond well to antiangiogenic drugs such as ramucirumab | ||||
| Clinical Availability Status | Clinical use (anti-vascular therapy screening) : It is used to predict the efficacy of ramucirumab, apatinib and other anti-vascular drugs | ||||
| Notes and Dynamics | The core marker of anti-angiogenic therapy, combined with chemotherapy can improve the prognosis of patients with advanced gastric cancer. The serum VEGF level can be used to dynamically monitor the treatment response, and the resistance mechanism (such as FGFR amplification and Ang2 high expression) is the focus of current research | ||||
| Biomarker | TMB (Tumor mutation burden) | Full name | Tumor Mutation Burden | Molecular Type | Genomic signatures (DNA) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Prediction, Prognosis | ||
| Disease(or Constitution) | Gastric Cancer | Disease Subtypes | Intestinal-type gastric cancer/diffuse gastric cancer | ||
| Organ | Stomach | Test Sample / Technology Platform | Tumor tissue (NGS), circulating tumor DNA (ctDNA, NGS) | ||
| Pathobiological Mechanisms | It refers to the number of somatic mutations per million bases in the tumor genome. Gastric cancer with high TMB (TMB-H) produces more neoantigen due to mutation accumulation, which can activate stronger anti-tumor immune response | ||||
| Clinical Availability Status | Clinical research stage: most of them are in phase II/III clinical verification, and some centers have used it as a reference index for immunotherapy | ||||
| Notes and Dynamics | Tmb-h and MSI-H/dMMR partially overlap in gastric cancer, but there is also an independent TMB-H population. Dynamic monitoring of TMB by ctDNA can reflect the evolution of tumor mutation in real time and guide the adjustment of immunotherapy. Standardized detection Panel is the future direction | ||||