Long non-coding RNAs as prognostic markers in human breast cancer

// Hairong Liu 1, 2 , Juan Li 1, 3 , Pratirodh Koirala 1, 4 , Xianfeng Ding 1, 5 , Binghai Chen 1, 6 , Yiheng Wang 7 , Zheng Wang 7 , Chuanxin Wang 3 , Xu Zhang 8 , Yin-Yuan Mo 1, 9 1 Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA 2 Department of Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China 3 Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shangdong Province, China 4 Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS, USA 5 College of Life Science, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China 6 Department of Urology, Affiliated Hospital of Jiangsu University, Jiangsu, Zhenjiang, China 7 School of Computing, University of Southern Mississippi, Hattiesburg, MS, USA 8 Center of Biostatistics and Bioinformatics, Department of Preventive Medicine, University of Mississippi Medical Center, Jackson, MS, USA 9 Department of Pharmacology/Toxicology, University of Mississippi Medical Center, Jackson, MS, USA Correspondence to: Xu Zhang, e-mail: xzhang2@umc.edu Yin-Yuan Mo, e-mail: ymo@umc.edu 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 ABSTRACT 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.