Zhao et al. [32] analyzed the expression of the transmembrane protein CD133 in GC, because it was described that CD133 is overexpressed in various solid tumors [33]. They found that CD133 Ibrutinib ic50 was overexpressed in more than 55% of GC and has a positive correlation with the expression of Ki-67. In another study, Anami et al. [34] found an overexpression

of the membrane protein desmocollin-2 (DSC2) in intestinal-type GC. Interestingly, they showed that expression of DSC2 was induced by CDX2, suggesting that expression of desmocollin-2 could be a key regulator for GC with intestinal phenotype. One transmembrane protein for which a new targeted compound is being studied in clinical trials on solid tumors is P-cadherin. Kim et al. [35] reported recently that P-cadherin is not expressed in normal

gastric mucosa but is overexpressed in GC, especially in tumors of the intestinal type. The authors reported that the increased expression of P-cadherin in GC was found to be significantly correlated with promoter hypomethylation. Another member of the cadherin superfamily, CDH17, was also reported by Lee et al. [36] as a promising marker for early-stage gastric cancer. Also according to Lee et al., CDH17 expression was positively find more associated with a good prognosis. Hyaluronic acid (HA) is a component of the extracellular matrix. In cancerous tissue, HA is greatly secreted from stromal fibroblasts in response to factors medchemexpress derived from tumor cells [37]. The two most well-known cell receptors for HA are CD168 and CD44 [38]. In a recent study, Ishigami et al. [39] reported the overexpression of CD168 in a panel of GC cases. According to these authors, CD168 positivity was significantly associated with the depth of invasion and metastasis of GC, an association that was previously reported for other types of cancer [40].

In a different study, da Cunha et al. [41] described the de novo expression of a CD44 variant (CD44v6) in GC. Noteworthy, they observed that CD44v6 was rarely expressed in normal gastric mucosa but was increasingly expressed in premalignant and malignant lesions. A recent study by Ishimoto et al. [42] sheds light about some roles of CD44 variants (CD44v) expression in gastrointestinal tumors. Ishimoto et al. found that CD44v controls the intracellular level of reduced glutathione (GSH), and cancer cells that express more CD44v showed an enhanced capacity for GSH synthesis and defence against reactive oxygen species, promoting tumor growth. Matrix metalloproteinases (MMP), a family of zinc-dependent endopeptidases, are involved in various physiological and pathological processes, such as extracellular matrix degradation, tissue remodeling, inflammation, and tumor invasion and metastasis [43].