Association Between EphA1 and Tumor Microenvironment in Gastric Carcinoma and its Clinical Significance.

BACKGROUND With the growing global burden of gastric carcinoma (GC) and the urgent need for biomolecular targeted therapies, this study aimed to elucidate the relationship between EphA1 and the tumor microenvironment (focusing primarily on the key inflammatory cytokines IL-6 and tumor angiogenic cytokine VEGF) to identify a new potential therapeutic target. MATERIAL AND METHODS IHC and qRT-PCR were performed to quantify the protein and gene expression levels of EphA1, IL-6, and VEGF in normal mucosal tissues, carcinoma tissues, and paracarcinomatous tissues from 57 GC patients. Spearman's rank correlation test was performed to determine the relationship between EphA1, IL-6, and VEGF expression levels. The relationships of EphA1 with clinicopathologic parameter and survival in GC patients were also evaluated. RESULTS The protein and gene expression levels of EphA1 were all attenuated gradually from carcinoma tissues to paracarcinomatous tissues and then to normal mucosal tissues in GC patients. Additionally, significant correlations between the overexpression of EphA1 with aggressive clinicopathological features and shorter survival time of GC patients were verified. In particular, we found a significant positive correlation between the expression of EphA1 and tumor microenvironment hallmark proteins IL-6 and VEGF in carcinoma tissues and paracarcinomatous tissues. CONCLUSIONS EphA1 can promote the occurrence and development of GC by its selective high expression in cancer tissues and its relationship with malignant clinical features and prognosis of GC patients. The underlying potential mechanism appears to involve enhancement of the tumor microenvironment, which via drives the expression of tumor microenvironment hallmark proteins IL-6 and VEGF.

Prognostic Value of Upregulation of Myristoylated Alanine-Rich C-Kinase Substrate in Gastric Cancer.

BACKGROUND Accumulating evidence suggests a connection of Myristoylated alanine-rich C-kinase substrate (MARCKS) with several physiological and pathological processes. However, the relevance of MARCKS in gastric cancer (GC) needs to be elucidated. MATERIAL AND METHODS The abundance of MARCKS in GC tissues was assessed using techniques of immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR). Moreover, the MARCKS expression profile in the TCGA database was analyzed through an online website analysis. We also investigated MARCKS function using cell wounding and Matrigel invasion assays. RESULTS TCGA analysis and our data suggest that transcript abundance and protein level of MARCKS was higher in GC tumor samples compared with peri-tumor tissues. There was a remarkable association of upregulated MARCKS with the cell differentiation (P<0.001), T stage (P=0.034), and N stage (P=0.002) followed by advanced TNM phase (P=0.008). Furthermore, it was predicted that higher expression of MARCKS is linked to poor overall survival (P=0.015) and disease-free survival (P=0.020), and that high levels of MARCKS function as an independent prognostic marker, as shown by multivariate Cox regression analysis in prediction of poor overall (HR=0.408; 95% confidence interval=0.247-0.674; P<0.001) and disease-free survival rates (HR=0.525; 95% confidence interval=0.216-0.584; P<0.001). GC cells showed significant reduction in cell migration and invasion upon depletion of MARCKS as noted through Matrigel invasion and cell wounding assays. Further analyses showed that silencing MARCKS impeded the epithelial-mesenchymal transition (EMT). CONCLUSIONS Our study indicates that elevated expression of MARCKS is significantly associated with metastatic capability of GC cells, and MARCKS overexpression can serve as a biomarker of GC poor prognosis.

High Expression of Peroxiredoxin 1 Is Associated with Epithelial-Mesenchymal Transition Marker and Poor Prognosis in Gastric Cancer.

BACKGROUND Recent studies show that peroxiredoxin 1 (Prdx1) contributes to the progression and poor prognosis of carcinoma through multiple mechanisms. However, there is little information on its expression and prognostic value in gastric cancer. This study investigated the expression of Prdx1 in gastric cancer, along with evaluating its clinical-pathological and prognostic importance. MATERIAL AND METHODS A total of 189 pairs of gastric cancer and paracarcinomatous tissues were assessed for Prdx1 expression and its association with clinical characteristics. The molecular mechanism was further investigated through in vitro experimentation. RESULTS The mRNA and protein levels of Prdx1 in the GC tissues were higher than in the peri-tumor tissues. We also found that high Prdx1 expression was positively correlated with the lymph node invasion and poor prognosis. It also served as an autonomous prognostic factor for patients with gastric cancer. Moreover, Prdx1 regulates the invasion and metastasis of GC cell lines through inhibiting E-Ca expression. CONCLUSIONS Prdx1 can promote epithelial-mesenchymal transition and gastric cancer progression. Therefore, it might be a therapeutic target and prognostic indicator for gastric cancer patients.