Altered expression of EphA2 and EphrinA1 associated with prognosis of malignant glioma patients

Objective Malignant gliomas display over-expression of the receptor tyrosine kinase EphA2. However,expression levels of the EphA2 ligand,EphrinA1,have not been fully elucidated. This study aims to determine the expression of EphA2 / EphrinA1 in detail,and further detect the predictive

Prognostic Significance of Autophagy-Related Proteins Expression in Resected Human Gastric Adenocarcinoma

Gastric adenocarcinoma（GC） is one of the most common malignancies in the world and one of the most frequent causes of cancer-related death. Autophagy is a highly regulated catabolic pathway responsible for the degradation of long-lived proteins and damaged intracellular organelles. However, the mechanism and guiding significance of autophagy in the development and progression of GC have remained to be elucidated. This study aimed to explore the clinicopathological significances and prognostic values of autophagy-related proteins AMBRA1 and Beclin-1 in GC. Quantum dots based immunofluorescence histochemistry（QDs-IHC） was performed to observe the expression of AMBRA1 and Beclin-1 proteins in the tissue microarrays including 163 specimens of GC and 20 noncancerous gastric tissues. Simultaneously, AMBRA1 and Beclin-1 proteins were detected by Western blotting in the 10 fresh GC and corresponding normal gastric tissues. The results showed that the expression levels of both AMBRA1 and Beclin-1 proteins were higher in GC tissues than in noncancerous gastric tissues by QDs-IHC and Western blotting（P〈0.05）. High AMBRA1 expression was detected in 90 of 163（55.2%） GCs and high Beclin-1 expression was detected in 83 of 163（50.9%） GCs. High AMBRA1 expression was closely related to depth of invasion, and lymph nodes metastasis（P〈0.05）. High expression of Beclin-1 protein was correlated with tumor grade（P〈0.05）. Positive correlation was observed between AMBRA1 and Beclin-1. Survival analysis indicated the high expression of AMBRA1 and Beclin-1 was an independent factor in predicting poor overall survival（OS） of GC patients. These findings suggest the high expression of AMBRA1 and Beclin-1 proteins is significantly correlated with GC progression. High AMBRA1 and Beclin-1 expression heralds worse outcome of GC patients, suggesting a novel candidate prognostic marker and a therapeutic target for GC.

A glycolysis-based ten-gene signature correlates with the clinical outcome, molecular subtype and IDH1 mutation in glioblastoma

Reprogrammed metabolism is a hallmark of cancer. Glioblastoma（GBM） tumor cells predominantly utilize aerobic glycolysis for the biogenesis of energy and intermediate nutrients. However, in GBM, the clinical significance of glycolysis and its underlying relations with the molecular features such as IDH1 mutation and subtype have not been elucidated yet. Herein, based on glioma datasets including TCGA（The Cancer Genome Atlas）, REMBRANDT（Repository for Molecular Brain Neoplasia Data） and GSE16011 we established a glycolytic gene expression signature score（GGESS） by incorporating ten glycolytic genes. Then we performed survival analyses and investigated the correlations between GGESS and IDH1 mutation as well as the molecular subtypes in GBMs. The results showed that GGESS independently predicted unfavorable prognosis and poor response to chemotherapy of GBM patients. Notably, GGESS was high in GBMs of mesenchymal subtype but low in IDH1-mutant GBMs. Furthermore, we found that the promoter regions of tumor-promoting glycolytic genes were hypermethylated in IDH1-mutant GBMs.Finally, we found that high GGESS also predicted poor prognosis and poor response to chemotherapy when investigating IDH1-wild type GBM patients only. Collectively, glycolysis represented by GGESS predicts unfavorable clinical outcome of GBM patients and is closely associated with mesenchymal subtype and IDH1 mutation in GBMs.