A long non-coding RNA signature to improve prognosis prediction of colorectal cancer

Ye Hu, Hao Yan Chen, Chen Yang Yu, Jie Xu, Ji Lin Wang, Jin Qian, Xi Zhang, Jing Yuan Fang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

132 Scopus citations

Abstract

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 lncRNAmining 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 sixlncRNA signature, the test series patients could be classified into high-risk and lowrisk 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.

Original languageEnglish (US)
Pages (from-to)2230-2242
Number of pages13
JournalOncotarget
Volume5
Issue number8
DOIs
StatePublished - Apr 2014

Keywords

  • Colorectal cancer
  • GSEA
  • LncRNAs
  • Survival

ASJC Scopus subject areas

  • Oncology

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