Abstract
PurposeThe present study investigated the clinical significance of transmembrane protease, serine 4(TMPRSS4) and extracellular signal-regulated kinases 1 (Erk1) in the development, progression and metastasis of gastric cancer.MethodsImmunohistochemistry was employed to analyze TMPRSS4 and Erk1 expression in 436 gastric cancer cases and 92 non-cancerous human gastric tissues.ResultsProtein levels of TMPRSS4 and Erk1 were up-regulated in gastric cancer lesions compared with adjacent noncancerous tissues. High expression of TMPRSS4 correlated with age, size, Lauren’s classification, depth of invasion, lymph node and distant metastases, regional lymph node stage and TNM stage, and also with expression of Erk1. In stages I, II and III, the 5-year survival rate of patients with high TMPRSS4 expression was significantly lower than in patients with low expression. Further multivariate analysis suggests that up-regulation of TMPRSS4 and Erk1 were independent prognostic indicators for the disease, along with depth of invasion, lymph node and distant metastasis and TNM stage.ConclusionsExpression of TMPRSS4 in gastric cancer is significantly associated with lymph node and distant metastasis, high Erk1 expression, and poor prognosis. TMPRSS4 and Erk1 proteins could be useful markers to predict tumor progression and prognosis of gastric cancer.
Highlights
Type II transmembrane serine proteases (TTSPs) have been recognized as a new subfamily of serine proteases with a proteolytic domain, a transmembrane domain, a short cytoplasmic domain and a stem region of variable length that contains modular structural domains[1,2]
The current study examined the expression of TMPRSS4 and Extracellular signalregulated kinase 1 (Erk1) in 436 surgical specimens of gastric cancer by immunohistochemistry, to explore the possible correlation of TMPRSS4 and Erk1 expression with clinicopathological variables, and to determine the prognostic value of TMPRSS4 and Erk1 expression
High expression of TMPRSS4 correlated with age, size, Lauren’s classification, depth of invasion, lymph node and distant metastases, regional lymph node stage and TNM stage (P,0.05) (Table 1)
Summary
Type II transmembrane serine proteases (TTSPs) have been recognized as a new subfamily of serine proteases with a proteolytic domain, a transmembrane domain, a short cytoplasmic domain and a stem region of variable length that contains modular structural domains[1,2]. Most TTSPs have been implicated in tumor development and progression, mainly based on their dysregulated expression. Transmembrane protease, serine 4(TMPRSS4) is a TTSP that is highly expressed in pancreatic, thyroid, lung and colorectal cancers[3,4]. Extracellular signalregulated kinase 1 (Erk1) is a member of the MAP kinase family and acts in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals [6]. The biological functions and clinical significance of TMPRSS4 and Erk in gastric cancer are not understood. The current study examined the expression of TMPRSS4 and Erk in 436 surgical specimens of gastric cancer by immunohistochemistry, to explore the possible correlation of TMPRSS4 and Erk expression with clinicopathological variables, and to determine the prognostic value of TMPRSS4 and Erk expression
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