Abstract
Gastric cancer remains a malignancy with poor survival outcome. We herein report that GSE1, a proline-rich protein, possesses a role in the progression of human gastric cancer. The expression of GSE1 was observed to be much higher in human gastric cancer tissues compared with normal gastric tissues, and GSE1 expression correlated positively with lymph node metastasis, histological grade, depth of invasion, and clinical stage in gastric cancer patients. Moreover, GSE1 expression was also associated with decreased post-operative relapse-free survival and overall survival in the cohort. The forced expression of GSE1 in gastric cancer cell lines resulted in increased cell proliferation, increased colony formation, enhanced cell migration, and invasion. Furthermore, forced expression of GSE1 also increased tumor size and enhanced lung metastasis in xenograft models. The depletion of endogenous GSE1 with shRNAs decreased the oncogenicity and invasiveness of gastric cancer cells both in vitro and in vivo In addition, GSE1 was determined to be a direct target of miR-200b and miR-200c. Furthermore, GSE1 positively regulated the downstream gene SLC7A5 (also known as LAT-1), which was scanned and verified from mRNA sequencing. GSE1 therefore possesses an oncogenic role in human gastric cancer, and targeted therapeutic approaches to inhibit GSE1 function in gastric cancer warrant further consideration.
Highlights
Gastric cancer remains a malignancy with poor survival outcome
The depletion of GSE1 in gastric cancer cells reduced the oncogenic properties of gastric cancer cells both in vitro and in vivo
The expression of GSE1 protein was higher in gastric cancer tissues compared with normal gastric tissues, and the expression level of GSE1 positively associated with lymph node metastasis, histological grade, depth of invasion, and clinical stage in gastric cancer patients
Summary
We first determined the expression of GSE1 in 100 human gastric cancer tissues and 100 normal gastric tissues using immune histochemistry. 51 of 100 cases of normal gastric tissues were negative for expression of GSE1, 34 of 100 cases exhibited low expression of GSE1, 10 of 100 cases exhibited moderate expression of GSE1, and 5 of 100 cases exhibited high expression of GSE1. 17 of 100 cases of gastric cancer tissues were negative for expression of GSE1, 27 of 100 cases exhibited low expression of GSE1, 37 of 100 cases exhibited moderate expression of GSE1, and 19 of 100 cases exhibited high expression of GSE1 (p Ͻ 0.001). We examined the association of GSE1 expression with clinicopathological parameters, including patients’ age, gender, tumor size, lymph node metastasis, histological grade, depth of invasion, and clinical stage. The expression of GSE1 was positively correlated with patient lymph node metastasis (p ϭ 0.001), histological grade (p ϭ 0.037), depth of invasion (p ϭ 0.008), and clinical stage (p ϭ 0.001). These gastric cancer patients were followed up for more than 5 years, and the association of GSE1 expression
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