Research progress on exosomal proteins as diagnostic markers of gastric cancer (review article)

Abstract

Gastric cancer (GC) is one of the most common types of tumors and the most common cause of cancer mortality worldwide. The diagnosis of GC is critical to its prevention and treatment. Available tumor markers are the crucial step for GC diagnosis. Recent studies have shown that proteins in exosomes are potential diagnostic and prognostic markers for GC. Exosomes, secreted by cells, are cup-shaped with a diameter of 30–150 nm under the electron microscope. They are also surrounded by lipid bilayers and are widely found in various body fluids. Exosomes contain proteins, lipids and nucleic acid. The examination of exosomal proteins has the advantages of quickness, easy sampling, and low pain and cost, as compared with the routine inspection method of GC, which may lead to marked developments in GC diagnosis. This article summarized the exosomal proteins with a diagnostic and prognostic potential in GC, as well as exosomal proteins involved in GC progression.

Recent Trends and Advancements in the Diagnosis and Management of Gastric Cancer

“…TGF-β1 is an immunosuppressive cytokine that has been detected in exosomes of GC patients and was found to be correlated with lymphatic metastasis [ 52 , 53 ]. Tripartite motif 3 (TRIM3) is a protein that normally inhibits the proliferation of GC cells; it has been found that the levels of TRIM3 in serum exosomes of patients with GC are lower than those of healthy controls, making it a potential diagnostic biomarker for GC [ 54 ]. Gastrokine-1 (GKN-1) is another exosomal cargo protein involved in regulating the immune response and inhibiting proliferation of GC cells [ 54 ].…”

“…Tripartite motif 3 (TRIM3) is a protein that normally inhibits the proliferation of GC cells; it has been found that the levels of TRIM3 in serum exosomes of patients with GC are lower than those of healthy controls, making it a potential diagnostic biomarker for GC [ 54 ]. Gastrokine-1 (GKN-1) is another exosomal cargo protein involved in regulating the immune response and inhibiting proliferation of GC cells [ 54 ]. Yoon et al found that healthy controls had significantly higher serum GKN1 levels than GC patients (6.34 ng/μL vs. 3.48 ng/μL, p < 0.0001), suggesting it to be another potential biomarker for GC.…”

“…Heat shock proteins (HSP) 60 and 70 have been found in higher concentration within exosomes derived from malignant ascites in GC patients compared with exosomes derived from ascites in non-GC patients [ 55 ]. HSP-60 and 70 aid in the immune response against GC by promoting the maturation of dendritic cells, inducing a cytotoxic T-lymphocyte response against the tumor [ 54 ]. These exosomal proteins have yet to be studied in large cohort clinical trials and hence their applicability in the clinical setting is yet to be known.…”

Structure–activity relationship and in silico development of c‐Met kinase inhibitors

“…The c‐Met kinase belongs to the receptor tyrosine kinase (RTK) family and is expressed primarily on the surfaces of various epithelial cells 1 . Aberrant expression of c‐Met has been found in gastric cancer (GC) in multiple clinical and preclinical studies, making it a key cancer biomarker 2–3 . Abnormal amplification, deregulation, and genetic mutations in the MET encoder gene have also been reported to cause the overexpression of c‐Met 4 .…”

“…1 Aberrant expression of c-Met has been found in gastric cancer (GC) in multiple clinical and preclinical studies, making it a key cancer biomarker. [2][3] Abnormal amplification, deregulation, and genetic mutations in the MET encoder gene have also been reported to cause the overexpression of c-Met. 4 Structurally, c-Met is a 1390 amino acid long-chain protein and is a heterodimer of an extracellular chain α, linked to a transmembrane chain β with a single disulfide bridge.…”