A long non-coding RNA signature to improve prognosis prediction of colorectal cancer
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Ye Hu1,*, Hao-Yan Chen1,*, Chen-Yang Yu1,*, Jie Xu1, Ji-Lin Wang1, Jin Qian1, Xi Zhang2, Jing-Yuan Fang1
1 Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institution of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; State Key Laboratory of Oncogene and Related Genes., Shanghai, China.
2 Departments of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center, Houston, TX,USA
* These authors contribute equally to this work.
Jing-Yuan Fang, email:
Hao-Yan Chen , email:
Jie Xu, email:
Keywords:colorectal cancer, lncRNAs, survival, GSEA
Received: February 20, 2014 Accepted: April 11, 2014 Published: April 11, 2014
Increasing evidence suggests long non-coding RNAs (lncRNAs) are frequently aberrantly expressed in cancers, however, few related lncRNA signatures have been established for prediction of cancer prognosis. We aimed to develop a lncRNA signature to improve prognosis prediction of colorectal cancer (CRC). Using a lncRNA-mining approach, we performed lncRNA expression profiling in large CRC cohorts from Gene Expression Ominus (GEO), including GSE39582 test series(N=436), internal validation series (N=117); and two independent validation series GSE14333 (N=197) and GSE17536(N=145). We established a set of six lncRNAs that were significantly correlated with the disease free survival (DFS) in the test series. Based on this six-lncRNA signature, the test series patients could be classified into high-risk and low-risk subgroups with significantly different DFS (HR=2.670; P<0.0001). The prognostic value of this six-lncRNA signature was confirmed in the internal validation series and another two independent CRC sets. Gene set enrichment analysis (GSEA) analysis suggested that risk score positively correlated with several cancer metastasis related pathways. Functional experiments demonstrated three dysregulated lncRNAs, AK123657, BX648207 and BX649059 were required for efficient invasion and proliferation suppression in CRC cell lines. Our results might provide an efficient classification tool for clinical prognosis evaluation of CRC.
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