Abstract
Gastric cancer (GC) is a frequently occurring malignancy with high mortality rates. However, the underlying mechanism of GC progression is not very clear. The aim of this study is to reveal the inherent molecular mechanism and develop potential therapeutic targets for advanced GC. The microfibril-associated glycoprotein 1 (MAGP1), identified as a potential oncogene, was found upregulated in GC tissues and high MAGP1 expression was associated with aggressive clinicopathological features. Furthermore, the multivariate Cox regression analysis showed that high MAGP1 expression was an independent predictor of poor prognosis (HR = 2.37, 1.07–5.24; P = 0.033). Mechanistically, MAGP1 promoted the migration and invasiveness of GC cells. In addition, the genes co-expressed with MAGP1 were primarily enriched in focal adhesion and PI3K-Akt pathways. MAGP1 overexpression enhanced the phosphorylation of FAK, AKT, and mTOR, whereas its knockdown also inactivated these factors. Furthermore, the AKT inhibitor suppressed the phosphorylation of AKT, FAK, and mTOR in recMAGP1-treated AGS cells, as well as their migration and invasion capacities. Finally, correlation analysis indicated that MAGP1 is involved in AKT signaling in GC, and is clinically relevant. Taken together, MAGP1 is a promising prognostic marker and potential therapeutic target for advanced GC.
Highlights
Gastric cancer (GC) is an aggressive gastrointestinal malignancy with high incidence and mortality rates worldwide, especially in Asia [1,2,3]
The GC samples retrieved from The Cancer Genome Atlas (TCGA) were divided into the metastatic [TNM stage IV, N = 27) and early stage (TNM stage IA, N = 16) groups, in order to identify the putative differentially expressed genes (DEGs) involved in GC metastasis
We found that Microfibril associated glycoprotein 1 (MAGP1) expression was upregulated in GC tissues and correlated with lymph node metastasis and poor prognosis
Summary
Gastric cancer (GC) is an aggressive gastrointestinal malignancy with high incidence and mortality rates worldwide, especially in Asia [1,2,3]. GC patients are often diagnosed at the advanced stages due to lack of characteristic early symptoms, and frequent recurrence with distant metastasis is seen even after surgical resection, due to undetected micro-metastases [4, 5]. For locally advanced GC, adjuvant or neoadjuvant therapy is usually implemented in combination with surgery. Targeted therapy has improved the prognosis of various tumors, such as breast cancer, non-small cell lung cancer and colorectal cancer [7]. Novel molecular targeting agents that were effective in other malignancies have failed against GC. It is essential to identify novel biomarkers and therapeutic targets for advanced GC
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