High BIM mRNA levels are associated with longer survival in advanced gastric cancer

Abstract

Abstract. Chemotherapy drugs, including 5-fluorouracil (5-FU), oxaliplatin and docetaxel, are commonly used in the treatment of gastric cancer (GC). Apoptosis-relevant genes may be associated with drug resistance. In the present study, the messenger RNA (mRNA) expression levels of B-cell lymphoma 2 interacting mediator of cell death (BIM), astrocyte elevated gene-1 (AEG-1) and AXL receptor tyrosine kinase (AXL) were investigated in 131 advanced GC samples, and the expression levels of these genes were correlated with patients' overall survival (OS). All 131 patients received first-line FOLFOX combination chemotherapy with folinic acid and 5-FU, in which 56 patients were further treated with second-line docetaxel-based chemotherapy. A correlation between the mRNA expression levels of BIM and AEG-1 was observed (r s =0.30; P=0.002). There was no association between the mRNA expression levels of any of the individual genes analyzed and OS in patients only receiving first-line FOLFOX chemotherapy. In a subgroup of patients receiving docetaxel-based second-line chemotherapy, those with high or intermediate levels of BIM exhibited a median OS of 18.2 months [95% confidence interval (CI), 12.8-23.6], compared with 9.6 months (95% CI, 8.9-10.3) in patients with low BIM levels (P=0.008). However, there was no correlation between the mRNA expression levels of AEG-1 or AXL and OS. The risk of mortality was higher in patients with low BIM mRNA levels than in those with high or intermediate BIM mRNA levels (hazard ratio, 2.61; 95% CI, 1.21-5.62; P=0.010). Therefore, BIM may be considered as a biomarker to identify whether patients could benefit from docetaxel-based second-line chemotherapy in GC.

Combined Action of Anti-MUC1 Monoclonal Antibody and Pyrazole-Platinum(II) Complexes Reveals Higher Effectiveness towards Apoptotic Response in Comparison with Monotherapy in AGS Gastric Cancer Cells

“…Following pro-apoptotic events, Bim translocates to the mitochondria, where it is essential to mediate the release of cytochrome c, which in turn activates caspase-9 [ 38 ]. Additionally, Bim upregulation has been reported to affect the chemotherapy response [ 39 ]. Therefore, the combined action of PtPz6 and anti-MUC1 showing inhibitory effect toward Akt mRNA revealed in our study seems to be an effective therapy, promoting activation of apoptosis.…”

Sorcin induces gastric cancer cell migration and invasion contributing to STAT3 activation

“…Gastric cancer is the second leading cause of cancer-associated death worldwide [ 1 , 2 ]. Approximately 40% of all GC cases occur in China and these are often diagnosed in the advanced stages [ 3 , 4 ]. The 5 year survival rate was 28% in 2014 [ 5 ].…”

Proteomic Signatures of Diffuse and Intestinal Subtypes of Gastric Cancer

“…The chemotherapeutic agents used, dose and duration of either chemotherapy and/or radiotherapy administered to the patients in the TCGA dataset is not available. In a study by Wu et al, where they studied the correlation between mRNA expression of B-cell lymphoma 2 interacting mediator of cell death ( BIM ), astrocyte elevated gene-1 ( AEG-1 ) and AXL receptor tyrosine kinase ( AXL ) and OS in gastric cancer, no association between mRNA expression and OS for any of these genes following first-line chemotherapy with folinic acid, 5-fluorouracil (5-FU), and oxaliplatin (FOLFOX) was found [ 121 ]. However, they did notice a strong association between mRNA expression of BIM and OS in a subset of patients who received second-line docetaxel-based chemotherapy.…”