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 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.
Highlights
As the third leading culprit in cancer incidence worldwide [1], colorectal cancer (CRC) continues to pose significant diagnostic, prognostic and therapeutic tribulations for clinicians
The results showed that the six-long non-coding RNAs (lncRNAs) risk score remained to be significantly associated with disease free survival (DFS) when adjusted by American Joint Committee on Cancer (AJCC) stage and other variables in every cohort (Table 2)
The conventional view of gene regulation in biology has centered around protein-coding genes until the discovery of thousands of lncRNAs
Summary
As the third leading culprit in cancer incidence worldwide [1], CRC continues to pose significant diagnostic, prognostic and therapeutic tribulations for clinicians. Many studies have exploited microarray technology to investigate gene expression profiles (GEPs) in CRC in recent years, but only a small subset demonstrates clear prognostic significance [5,6,7,8,9,10]. Molecular markers such as mutations in Kirsten ras gene (KRAS) and BRAF as well as chromosome instability (CIN) and microsatellite instability (MSI) have been systematically www.impactjournals.com/oncotarget analysed for prognostic potential in CRC[11].
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