Expression profile of long non-coding RNAs in pancreatic cancer and their clinical significance as biomarkers
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Yingxue Wang1,*, Zhihua Li2,*, Shangyou Zheng1,*, Yu Zhou1, Lei Zhao3, Huilin Ye1, Xiaohui Zhao4, Wenchao Gao1, Zhiqiang Fu1, Quanbo Zhou1, Yimin Liu4, Rufu Chen1
1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Hepatopancreatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China 510120
2Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China 510120
3Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China 510060
4Department of Radiation Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China 510120
*These authors have contributed equally to this work
Rufu Chen, e-mail: firstname.lastname@example.org
Keywords: long non-coding RNA, pancreatic cancer, splice variant, microarray, biomarker
Received: April 17, 2015 Accepted: September 21, 2015 Published: October 02, 2015
Long non-coding RNAs (lncRNAs) have shown great potential as powerful and non-invasive tumor markers. However, little is known about their value as biomarkers in pancreatic cancer (PC). We applied an Arraystar Human LncRNA Microarray which targeting 7419 lncRNAs to determine the lncRNA expression profile in PC and to screen the potential biomarkers. The most increased lncRNAs in PC tissues were HOTTIP-005, XLOC_006390, and RP11-567G11.1. Increased HOTTIP-005 and RP11-567G11.1 expression were poor prognostic factors for patients with PC (n = 144, p < 0.0001). The expression patterns of HOTTIP splice variants in PC were also detected. HOTTIP-005 and HOTTIP-001 were the first and second most increased HOTTIP splice variants, respectively. Plasma HDRF and RDRF (HOTTIP-005 and RP11-567G11.1 derived RNA fragments in plasma/serum) were present in stable form. Their levels were significantly increased in the patients with PC as compared to the healthy controls (n = 127 and 122 respectively, p < 0.0001) and the high levels were derived from PC. HDRF and RDRF levels are promising indicators for distinguishing patients with PC from those without PC. This study identified HOTTIP-005 and RP11-567G11.1 and their plasma fragments with the potential to be used as prognostic and diagnostic biomarkers of PC. Further large-scale prospective studies are needed to confirm our findings.
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