Emerging evidence of the molecular landscape specific for hematogenous metastasis from gastric cancer

Abstract

Gastric cancer (GC) is one of the most frequently diagnosed cancers in the world. Most GC patients are diagnosed when the cancer is in an advanced stage, and consequently, some develop metastatic lesions that generally cause cancer-related death. Metastasis establishment is affected by various conditions, such as tumor location, hemodynamics and organotropism. While digestive cancers may share a primary site, certain cases develop hematogenous metastasis with the absence of peritoneal metastasis, and vice versa. Numerous studies have revealed the clinicopathological risk factors for hematogenous metastasis from GC, such as vascular invasion, advanced age, differentiation, Borrmann type 1 or 2 and expansive growth. Recently, molecular mechanisms that contribute to metastatic site determination have been elucidated by advanced molecular biological techniques. Investigating the molecules that specifically participate in metastasis establishment in distinct secondary organs will lead to the development of novel biomarkers for patient stratification according to their metastatic risk and strategies for preventing and treating distinct metastases. We reviewed articles related to the molecular landscape of hematogenous metastasis from GC.

Keywords: Biomarker; Gastric cancer; Hematogenous metastasis; Hepatic metastasis; Molecular mechanism; Premetastatic niche.

Figure 1

Schema of molecules associated with each step of the establishment of hepatic metastasis from gastric cancer. VIM: Vimentin; GPR155: G protein-coupled receptor 155; HIF-1α: Hypoxia inducible factor-1 alpha; EGFL7: Epidermal growth factor-like domain-containing protein 7; CXCL1: C-X-C motif chemokine ligand 1; TIMP1: Tissue inhibitor of metallopeptidase 1; NFKB1/p105: Nuclear factor kappa B subunit 1; MAP1LC3: Microtubule associated protein 1 light chain 3; BECN1: Beclin1; SQSTM1/p62: Sequestosome 1; MFSD4: Major facilitator superfamily domain containing 4; PAK1: P21 (RAC1) activated kinase 1; VEGF-D: Vascular endothelial growth factor-D; TYMP: Thymidine phosphorylase.