Abstract
MicroRNAs play critical roles in tumor progression. Our recent study has indicated that microRNA-7 (miR-7) impairs autophagy-derived pools of glucose to suppress the glycolysis in pancreatic cancer progression. However, the roles of miR-7 in clinical significance and chemoresistance of pancreatic cancer remain unexplored. The aim of this study was to assess the expression of miR-7 in patients with pancreatic cancer and to evaluate the possibility of its usage as a prognostic molecular biomarker. MicroRNA array-based quantification analysis of 372 miRNAs was compared in serum between pancreatic cancer and healthy individuals, gemcitabine-sensitive and gemcitabine-resistance patients. We identified miR-7 showed the potential predictive power for gemcitabine-sensitive patients with pancreatic cancer. Then, the results were validated in pancreatic tissue microarray and The Cancer Genome Atlas (TCGA) dataset, demonstrating that lower miR-7 expression was correlated with more advanced tumor stages and worse prognosis in pancreatic cancer. The Cox proportional-hazards model analysis identified miR-7 to be an independent variable for prediction of the survival. Furthermore, the mechanistic exploration suggested the clinical significance of miR-7 involved its interference effect on autophagy and glycolysis in pancreatic cancer using pancreatic cancer tissue microarrays and TCGA data. Therefore, the results of the present study provide evidences that low microRNA-7 expression may contribute to tumor progression and poor prognosis in pancreatic cancer.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive primary pancreatic neoplasm and has the poorest prognosis among the solid tumor cancers
Our previous study has demonstrated that miR-7 could inhibit PDAC progression by repressing the activity of aerobic glycolysis via targeting autophagy in vitro and in vivo [9]; we further explored the possible role of miR-7 in clinical pancreatic cancer samples
Our study was the first time to systematically interrogate the function on autophagy and glycolysis and the clinical significance of miR-7 in pancreatic cancer
Summary
Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive primary pancreatic neoplasm and has the poorest prognosis among the solid tumor cancers. Despite of the dramatic progress in the treatment and understanding the molecular mechanisms of carcinogenesis, only approximately ~5% of patients with PDAC will live 5 years after the initial diagnosis [1]. The poor survival rate is attributed to the fact that the majority of patients are diagnosed at advanced disease stages, when pancreatic surgical resection is not possible. Gemcitabine has been proved to improve the median survival time and quality of life in advanced pancreatic cancer patients [2]. Gemcitabine has been widely used as a standard first-line therapy for pancreatic cancer. It is necessary to explore the biomarkers for early diagnosis, and for the Disease Markers prediction of therapy efficacy and prognosis, that could inform decision-making, facilitating personalized treatment, and an optimal clinical outcome
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