Long non-coding RNAs as prognostic markers in human breast cancer
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Hairong Liu1,2, Juan Li1,3, Pratirodh Koirala1,4, Xianfeng Ding1,5, Binghai Chen1,6, Yiheng Wang7, Zheng Wang7, Chuanxin Wang3, Xu Zhang8, Yin-Yuan Mo1,9
1Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA
2Department of Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China
3Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shangdong Province, China
4Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS, USA
5College of Life Science, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China
6Department of Urology, Affiliated Hospital of Jiangsu University, Jiangsu, Zhenjiang, China
7School of Computing, University of Southern Mississippi, Hattiesburg, MS, USA
8Center of Biostatistics and Bioinformatics, Department of Preventive Medicine, University of Mississippi Medical Center, Jackson, MS, USA
9Department of Pharmacology/Toxicology, University of Mississippi Medical Center, Jackson, MS, USA
Xu Zhang, e-mail: [email protected]
Yin-Yuan Mo, e-mail: [email protected]
Keywords: lncRNA, prognosis, breast cancer, biomarkers
Abbreviations: lncRNA, long non-coding RNA; lincRNA, long intergenic non-coding RNA; TCGA, The Cancer Genome Atlas; OS, overall survival; CNA, copy number alteration
Received: January 10, 2016 Accepted: February 18, 2016 Published: March 01, 2016
Long non-coding RNAs (lncRNAs) have been recently shown to play an important role in gene regulation and normal cellular functions, and disease processes. However, despite the overwhelming number of lncRNAs identified to date, little is known about their role in cancer for vast majority of them. The present study aims to determine whether lncRNAs can serve as prognostic markers in human breast cancer. We interrogated the breast invasive carcinoma dataset of the Cancer Genome Atlas (TCGA) at the cBioPortal consisting of ~ 1,000 cases. Among 2,730 lncRNAs analyzed, 577 lncRNAs had alterations ranging from 1% to 32% frequency, which include mutations, alterations of copy number and RNA expression. We found that deregulation of 11 lncRNAs, primarily due to copy number alteration, is associated with poor overall survival. At RNA expression level, upregulation of 4 lncRNAs (LINC00657, LINC00346, LINC00654 and HCG11) was associated with poor overall survival. A third signature consists of 9 lncRNAs (LINC00705, LINC00310, LINC00704, LINC00574, FAM74A3, UMODL1-AS1, ARRDC1-AS1, HAR1A, and LINC00323) and their upregulation can predict recurrence. Finally, we selected LINC00657 to determine their role in breast cancer, and found that LINC00657 knockout significantly suppresses tumor cell growth and proliferation, suggesting that it plays an oncogenic role. Together, these results highlight the clinical significance of lncRNAs, and thus, these lncRNAs may serve as prognostic markers for breast cancer.
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