Research Area

Gastric Cancer Biomarkers

Representative Biomarkers Full List of Biomarkers Tested Data-Supported Products

Gastric cancer (GC) ranks as the fifth most prevalent cancer globally, with over 1 million new cases in 2020, and stands as the fourth leading cause of cancer-related deaths. Its incidence is notably higher in males and significantly prevalent in Asian regions, particularly Japan and South Korea. The etiology of GC is multifaceted with Helicobacter pylori infection identified as a major risk factor. Despite the global decline in GC cases attributed to preventive measures against H. pylori infection, improved food preservation, and dietary changes, an uptick in proximal stomach and gastroesophageal junction cancers has been observed, linked to obesity and unmanaged gastroesophageal reflux disease. Advances in early detection, chemotherapy, and targeted therapies have contributed to a reduction in mortality rates over recent decades. However, the overall survival rate remains low, with a global 5-year survival rate of approximately 20%, underscoring the urgency for continued research and development of more effective treatment strategies.

Figure 1 Molecular characterization of subtypes of gastric carcinomas. CIN=chromosomally unstable tumors. EBV=Epstein-Barr virus-infected tumors. CIMP=CpG island methylation phenotype. MSI=microsatellite unstable tumors. (Van, 2016)

Representative Biomarkers of Gastric Cancer

CLDN18

Claudin-18 (CLDN18), a major component of tight junctions, plays a crucial role in maintaining barrier function and cellular polarity. The CLDN18 gene can produce two isoforms through alternative splicing: CLDN18.1 and CLDN18.2. Specifically, CLDN18.1 is primarily expressed in lung alveolar epithelium. While CLDN18.2 is predominantly expressed in gastric tissues, where it contributes to acid resistance and barrier integrity against H+ ions. Its aberrant expression in gastric cancer highlights its potential as a biomarker and therapeutic target. CLDN18.2's expression is significantly altered in gastric cancer, associated with tumor proliferation, invasion, and metastasis, making it a focal point for developing targeted therapies and immunotherapies. The dichotomous nature of CLDN18's function, acting either as a tumor suppressor or promoter based on its expression levels and tumor context, underscores the complexity of its roles in cancer biology and therapy.

Figure 2 The Binding Activity of Human CLDN18.2 with Anti-CLDN18.2 recombinant antibody. Activity: Measured by its binding ability in a functional ELISA. Immobilized Human CLDN18.2 (ZG-0141U) at 5 μg/mL can bind Anti-CLDN18.2 recombinant antibody, the EC50 is 6.554-27.87 ng/mL.

Figure 3 Mouse Anti-CLDN18 Recombinant Antibody (ZG-0155J) in IHC

Figure 3 Immunohistochemical analysis of paraffin-embedded Stomach-high magnification. 1. Antibody was diluted at 1:200 (4°C overnight). 2, Citrate buffer of pH6.0 was used for antigen retrieval. 3, Secondary Antibody was diluted at 1:200 (room temperature, 30min).

Figure 4 Human Anti-CLDN18 Antibody (ZG-0141U) in ELISA

Figure 4 The Binding Activity of Human CLDN18.2 with Anti-CLDN18.2 recombinant antibody. Activity: Measured by its binding ability in a functional ELISA. Immobilized Human CLDN18.2 (ZG-0141U) at 5 μg/mL can bind Anti-CLDN18.2 recombinant antibody, the EC50 is 6.554-27.87 ng/mL.

TFF1

Trefoil Factor Family 1 (TFF1), also known as pS2, is a small, secretory protein that plays a crucial role in the maintenance of gastrointestinal mucosal integrity by promoting epithelial cell migration, healing of mucosal injuries, and suppression of gastric acid secretion. Characterized by its trefoil domain, which facilitates interaction with mucins to stabilize the mucous gel layer, TFF1 is predominantly expressed in the gastric epithelium. TFF1 acts as a tumor suppressor gene. Its expression is frequently downregulated in gastric adenocarcinomas, often through promoter hypermethylation or deletion of its gene locus. This loss of TFF1 expression disrupts gastric mucosal healing processes and epithelial cell proliferation regulation, contributing to the pathogenesis and progression of gastric cancer. Moreover, TFF1's role in inhibiting gastric acid secretion indirectly affects the gastric environment, further influencing cancer development. Research has shown that restoring TFF1 expression in gastric cancer cells can suppress tumor growth and metastasis, highlighting its potential as a therapeutic target. Thus, TFF1 not only plays a significant role in maintaining gastric mucosal health but also in the prevention and progression of gastric cancer.

Breast cancer biomarkers at key points during disease progression

Figure 5 Immunohistochemical analysis of paraffin-embedded breast cancer-high magnification. 1. The antibody is diluted 1:200 (overnight at 4°C). 2. Use pH 6.0 citrate buffer for antigen retrieval. 3. Dilute the secondary antibody at 1:200 (room temperature, 30min).

Figure 6 Recombinant Mouse Anti-TFF1 Antibody (clone 6G1-7C8-9B6) in IHC-P

Figure 6 Immunohistochemical analysis of paraffin-embedded human breast carcinoma using Antibody to Estrogen-Inducible Protein pS2. High pressure and high temperature sodium citrate pH 6.0 for antigen retrieval.

Figure 7 Mouse Anti-TFF1 Recombinant Antibody (MOB-0230F) in IHC

Figure 7 Immunohistochemical analysis of paraffin-embedded human breast Paget's disease. 1. pS2 Antibody 1:200 dilution (4°C overnight). 2. Use pH 6.0 citrate buffer for antigen retrieval.

TLR2

Toll-like receptor 2 (TLR2) is a crucial component of the innate immune system, playing a pivotal role in recognizing pathogen-associated molecular patterns (PAMPs) from bacteria, fungi, and viruses, thereby initiating an immune response. Structurally, TLR2 is characterized by its leucine-rich repeat motifs, which facilitate the detection of microbial components, and a Toll/IL-1 receptor (TIR) domain, essential for downstream signaling. In the context of gastric cancer, TLR2's involvement is multifaceted, influencing both tumor promotion and suppression. On one hand, TLR2 activation can lead to chronic inflammation, a known risk factor for gastric cancer development, by inducing pro-inflammatory cytokines and chemokines that support a tumor-promoting microenvironment. This inflammation can drive the progression of precancerous lesions to malignant tumors in the gastric mucosa. On the other hand, TLR2 signaling has been implicated in anti-tumor immunity by enhancing the cytotoxic activity of immune cells against tumor cells. Despite its dual role, the precise mechanisms by which TLR2 influences gastric cancer pathogenesis remain an area of active research, highlighting its potential as a therapeutic target or biomarker in gastric cancer management.

Figure 8 ELISA analysis of ZG-0391F was performed by coating with human CEACAM5 Protein.

Full List of Gastric Cancer Biomarkers

Biomarker	Alternative Names	Gene ID	UniProt ID	Roles
ATAD2	ATPase Family, AAA Domain Containing 2; AAA Nuclear Coregulator Cancer-Associated Protein; ANCCA; EC 3.6.1.3; PRO2000; CT137	29028	A0A024R9G7	A large family of ATPases has been described, whose key feature is that they share a conserved region of about 220 amino acids that contains an ATP-binding site. The proteins that belong to this family either contain one or two AAA (ATPases Associated with diverse cellular Activities) domains. AAA family proteins often perform chaperone-like functions that assist in the assembly, operation, or disassembly of protein complexes. The protein encoded by this gene contains two AAA domains, as well as a bromodomain.
CLDN18	Claudin 18; Surfactant Associated Protein J; Surfactant, Pulmonary Associated Protein J; Surfactant Associated 5; Claudin-18; SFTA5; SFTPJ;	51208	P56856	This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets, and also play critical roles in maintaining cell polarity and signal transductions. This gene is upregulated in patients with ulcerative colitis and highly overexpressed in infiltrating ductal adenocarcinomas. PKC/MAPK/AP-1 (protein kinase C/mitogen-activated protein kinase/activator protein-1) dependent pathway regulates the expression of this gene in gastric cells. Alternatively spliced transcript variants encoding different isoforms have been identified.
DMBT1	DMBT1; Human DMBT1	1755	Q9UGM3
ETV1	ETS Variant 1; Ets-Related Protein 81; Ets Variant Gene 1; ER81; ETS Translocation Variant 1	2115	P50549	This gene encodes a member of the ETS (E twenty-six) family of transcription factors. The ETS proteins regulate many target genes that modulate biological processes like cell growth, angiogenesis, migration, proliferation and differentiation. All ETS proteins contain an ETS DNA-binding domain that binds to DNA sequences containing the consensus 5'-CGGA[AT]-3'. The protein encoded by this gene contains a conserved short acidic transactivation domain (TAD) in the N-terminal region, in addition to the ETS DNA-binding domain in the C-terminal region. This gene is involved in chromosomal translocations, which result in multiple fusion proteins including EWS-ETV1 in Ewing sarcoma and at least 10 ETV1 partners (see PMID: 19657377, Table 1) in prostate cancer. In addition to chromosomal rearrangement, this gene is overexpressed in prostate cancer, melanoma and gastrointestinal stromal tumor. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.
GKN1	Gastrokine 1; 18 KDa Antrum Mucosa Protein; BRICHOS Domain Containing 1; AMP-18; AMP18; CA11	56287	Q53YU7	The protein encoded by this gene is found to be down-regulated in human gastric cancer tissue as compared to normal gastric mucosa. [provided by RefSeq, Jul 2008]
PGA5	Pg5	5222	P00790	This gene encodes a protein precursor of the digestive enzyme pepsin, a member of the peptidase A1 family of endopeptidases. The encoded precursor is secreted by gastric chief cells and undergoes autocatalytic cleavage in acidic conditions to form the active enzyme, which functions in the digestion of dietary proteins. This gene is found in a cluster of related genes on chromosome 11, each of which encodes one of multiple pepsinogens. Pepsinogen levels in serum may serve as a biomarker for atrophic gastritis and gastric cancer. [provided by RefSeq, Jul 2015]
PSG2	CEA; PSG1; PSBG2	5670	P11465	Molecular cloning and analysis of several PSG genes has indicated that the PSGs form a subgroup of the carcinoembryonic antigen (CEA) gene family, which belongs to the immunoglobulin superfamily of genes. Members of the CEA family consist of a single N domain, with structural similarity to the immunoglobulin variable domains, followed by a variable number of immunoglobulin constant-like A and/or B domains.
SOX17	SOX17; SRY (Sex Determining Region Y)-Box 17; SRY-Related HMG-Box Transcription Factor SOX17; VUR3	64321	Q9H6I2	This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins.
TFF1	Trefoil Factor 1; Breast Cancer Estrogen-Inducible Protein; Polypeptide P1.A; Protein PS2; HP1.A; PNR-2; BCEI	7031	P04155	Members of the trefoil family are characterized by having at least one copy of the trefoil motif, a 40-amino acid domain that contains three conserved disulfides. They are stable secretory proteins expressed in gastrointestinal mucosa. Their functions are not defined, but they may protect the mucosa from insults, stabilize the mucus layer, and affect healing of the epithelium. This gene, which is expressed in the gastric mucosa, has also been studied because of its expression in human tumors. This gene and two other related trefoil family member genes are found in a cluster on chromosome 21. [provided by RefSeq, Jul 2008]
TLR2	CD282; TIL4	7097	O60603	The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. This protein is a cell-surface protein that can form heterodimers with other TLR family members to recognize conserved molecules derived from microorganisms known as pathogen-associated molecular patterns (PAMPs). Activation of TLRs by PAMPs leads to an up-regulation of signaling pathways to modulate the host's inflammatory response. This gene is also thought to promote apoptosis in response to bacterial lipoproteins. This gene has been implicated in the pathogenesis of several autoimmune diseases. Alternative splicing results in multiple transcript variants.
VSIG1	VSIG1; V-set and immunoglobulin domain containing 1; GPA34; dJ889N15.1; 1700062D20Rik; V-set and immunoglobulin domain-containing protein 1; glycoprotein A34; cell surface A33 antigen;	340547	Q86XK7	This gene encodes a member of the junctional adhesion molecule (JAM) family. The encoded protein contains multiple glycosylation sites at the N-terminal region, and multiple phosphorylation sites and glutamic acid/proline (EP) repeats at the C-terminal region. The gene is expressed in normal stomach and testis, as well as in gastric, esophageal and ovarian cancers. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Tested Data-Supported Products Targeting Gastric Cancer Biomarkers

CAT	Product Name	Biomarker	Assay	Image
MOB-0229F	Mouse Anti-TFF1 Recombinant Antibody (MOB-0229F)	TFF1	IHC
MOB-0230F	Mouse Anti-TFF1 Recombinant Antibody (MOB-0230F)	TFF1	IHC
ZG-0372C	Mouse Anti-PGA5 Recombinant Antibody (ZG-0372C)	PGA5	WB
ZG-0155J	Mouse Anti-CLDN18 Recombinant Antibody (ZG-0155J)	CLDN18	IHC
ZG-0156J	Mouse Anti-CLDN18 Recombinant Antibody (ZG-0156J)	CLDN18	IHC
ZG-0310J	Mouse Anti-ETV1 Recombinant Antibody (ZG-0310J)	ETV1	WB
ZG-146R	Mouse Anti-TLR2 Recombinant Antibody (ZG-146R)	TLR2	WB
ZG-0140U	Human Anti-CLDN18 Recombinant Antibody (clone 25E3)	CLDN18	FC
ZG-0141U	Human Anti-CLDN18 Recombinant Antibody (clone 9C2)	CLDN18	FC
VS3-FY389	Recombinant Mouse Anti-CLDN18 Antibody (clone 5F3-5G6-6B3)	CLDN18	IHC
VS3-FY1440	Recombinant Mouse Anti-TFF1 Antibody (clone 6G1-7C8-9B6)	TFF1	IHC-P