Abstract
BackgroundAltered expression of astrocyte elevated gene-1 (AEG-1) is associated with tumorigenesis and progression. The present study aimed to investigate the clinical and prognostic significance of AEG-1 expression in pancreatic ductal adenocarcinoma (PDAC).MethodsQuantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot analyses were employed to assess AEG-1 expression in three pancreatic cancer cell lines and normal pancreatic duct epithelial cells. qRT-PCR and immunohistochemical analyses were performed to detect AEG-1 expression in ten pairs of PDAC and normal pancreas tissues. Immunohistochemistry was then used to examine AEG-1 expression in paraffin-embedded tissues obtained from 105 patients, and its association with clinicopathological parameters including cancer classification was examined. Kaplan-Meier analysis was performed to study the survival rates of patients.ResultsExpression of AEG-1 mRNA and protein was markedly higher in pancreatic cancer cell lines than that in the normal pancreatic duct epithelial cells. AEG-1 expression was evidently upregulated in PDAC tissues compared to that of the matched distant normal pancreas tissues. qRT-PCR data revealed that the tumor/non-tumor ratio of AEG-1 expression was >1.5-fold (up to 6.5-fold). Immunohistochemical data showed that AEG-1 protein was detected in 98.09% (103/105) of PDAC tissues; and they were found to be associated with tumor size (P = 0.025), advanced clinical stage (P = 0.004), T classification (P = 0.006), N classification (P = 0.003), and M classification (P = 0.007). Furthermore, Kaplan-Meier analysis showed that patients with high AEG-1-expressed PDAC had shorter overall survival. A multivariate Cox regression analysis revealed that clinical stage, T classification, and AEG-1 expression were the independent prognostic predictors for PDAC.ConclusionsThis study suggests that AEG-1 protein was highly expressed in PDAC and associated with poor prognosis of the patients.
Highlights
Altered expression of astrocyte elevated gene-1 (AEG-1) is associated with tumorigenesis and progression
AsPC-1 was originally isolated from ascites of a patient with a Grade 2 pancreatic ductal adenocarcinoma (PDAC), while Mia Paca-2 and Panc-1 were from patients with poorly-differentiated (G3) primary PDAC, Capan-1 was isolated from a lymph node metastasis of a PDAC patients, BxPC-3 was isolated from a patient with pancreas ductal carcinoma in situ
Upregulation of AEG-1 expression in PDAC cells and tissues Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) data showed that all PDAC lines exhibited significantly higher levels of AEG-1 messenger ribonucleic acid (mRNA) compared to the normal pancreatic ductal epithelial cells, while Western blot analysis showed that AEG-1 protein was highly expressed in all pancreatic cancer cell lines including AsPC-1, Mia Paca-2, and Panc-1
Summary
Altered expression of astrocyte elevated gene-1 (AEG-1) is associated with tumorigenesis and progression. The present study aimed to investigate the clinical and prognostic significance of AEG-1 expression in pancreatic ductal adenocarcinoma (PDAC). AEG-1 can regulate human malignant glioma invasion through upregulation of matrix metalloproteinase-9 and activation of NF-κB signaling pathway [11,18,21,22]. These findings suggest that AEG-1 plays a dominant role in the development and progression of diverse cancers. The expression of AEG-1 messenger ribonucleic acid (mRNA) and protein in PDAC tissues were examined for association with clinicopathological and prognostic significance
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