Abstract

Long non-coding RNAs (lncRNAs) have been recently observed in various human cancers. However, the role of lncRNAs in pancreatic duct adenocarcinoma (PDAC) remains unclarified. The aim of this study was to detect the expression of lncRNA MALAT1 in PDAC formalin-fixed, paraffin embedded (FFPE) tissues and to investigate the clinical significance of the MALAT1 level. The expression of MALAT1 was examined in 45 PDAC and 25 adjacent non-cancerous FFPE tissues, as well as in five PDAC cell lines and a normal pancreatic epithelium cell line HPDE6c-7, using qRT-PCR. The relationship between MALAT1 level and clinicopathological parameters of PDAC was analyzed with the Kaplan-Meier method and Cox proportional hazards model. The relative level of MALAT1 was significantly higher in PDAC compared to the adjacent normal pancreatic tissues (p=0.009). When comparing the MALAT1 level in the cultured cell lines, remarkably higher expression of MALAT1 was found in aspc-1 PDAC cells compared with the immortal pancreatic duct epithelial cell line HPDE6c-7 (q=7.573, p<0.05). Furthermore, MALAT1 expression level showed significant correlation with tumor size (r=0.35, p=0.018), tumor stage (r=0.439, p=0.003) and depth of invasion (r=0.334, p=0.025). Kaplan-Meier analysis revealed that patients with higher MALAT1 expression had a poorer disease free survival (p=0.043). Additionally, multivariate analysis indicated that overexpression of MALAT1, as well as the tumor location and nerve invasion, was an independent predictor of disease-specific survival of PDAC. MALAT1 might be considered as a potential prognostic indicator and may be a target for diagnosis and gene therapy for PDAC.

Highlights

  • Pancreatic cancer (PC) is a highly malignant tumor with increasing incidence and mortality in the world (Canyilmaz et al, 2013; Siegel et al, 2013; Zahir et al, 2013), which leads to disproportionately high percentage (6.58%) of cancer-related deaths (Siegel et al, 2011)

  • Some well-defined Long non-coding RNAs (lncRNAs), including HOTAIR (Gupta et al, 2010; Kim et al, 2013; Nakagawa et al, 2013), MEG3 (Lu et al, 2013) and LOC285194 (Qi et al, 2013) have been reported to be strongly associated to survival of cancer patients, they have been determined as prognostic indicators for a delete certain types of cancers

  • MALAT1 was first discovered to be three folds higher expressed in metastasizing human non-small-cell lung carcinomas (NSCLCs) compared to the non-metastasizing tumor using RT-PCR by Ji P, et al in 2003

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Summary

Introduction

Pancreatic cancer (PC) is a highly malignant tumor with increasing incidence and mortality in the world (Canyilmaz et al, 2013; Siegel et al, 2013; Zahir et al, 2013), which leads to disproportionately high percentage (6.58%) of cancer-related deaths (Siegel et al, 2011). The 20μl RT reactions were primary transcripts (Schorderet and Duboule, 2011), performed using a Maxima First Strand cDNA Synthesis which is highly conserved among mammals and widely Kit (Fermentas, K1641, Canada) and were incubated expressed in normal mouse and human tissues, such as for 30min at 37°C, 5s at 85°C, and stabilized lung and pancreas, as well as in multiple cancer types, at 4°C. The disease specific survival (DSS) was study the relationship between MALAT1 expression defined as the length of time between the surgery and and clinicopathological parameters. 1, Bxpc-3, Aspc-1, Capan-1, Miapaca-2 and the human Results immortal pancreatic duct epithelial cell line HPDE6C-7 were purchased from the Institute of Biochemistry and Expression of MALAT1 in PADC tissues. ROC curve was performed to identify medium (wisent, China), while Bxpc-3, Aspc-1 and the diagnostic value of MALAT1 level in PDAC.

Venous invasion
Discussion
Findings
Newly diagnosed without treatment

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