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Mol Oncol. 2014 Dec;8(8):1393-403. doi: 10.1016/j.molonc.2014.05.010. Epub 2014 Jun 2.

Long noncoding RNA profiles identify five distinct molecular subtypes of colorectal cancer with clinical relevance.

Author information

1
State Key Laboratory of Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China. Electronic address: chenhaoyan@gmail.com.
2
State Key Laboratory of Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China. Electronic address: jiexu@yahoo.com.
3
State Key Laboratory of Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
4
Departments of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
5
State Key Laboratory of Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China. Electronic address: jingyuanfang@yahoo.com.

Abstract

Colorectal cancer (CRC) is a heterogeneous disease in terms of clinical behavior and response to therapy. Increasing evidence suggests that long noncoding RNAs (lncRNAs) are frequently aberrantly expressed in cancers, and some of them have been implicated in CRC biogenesis and prognosis. Using an lncRNA-mining approach, we constructed lncRNAs expression profiles in approximately 888 CRC samples. By applying unsupervised consensus clustering to LncRNA expression profiles, we identified five distinct molecular subtypes of CRC with different biological pathways and phenotypically distinct in their clinical outcome in both univariate and multivariate analysis. The prognostic significance of the lncRNA-based classifier was confirmed in independent patient cohorts. Further analysis revealed that most of the signature lncRNAs positively correlated with somatic copy number alterations (SCNAs). This lncRNAs-based classification schema thus provides a molecular classification applicable to individual tumors that has implications to influence treatment decisions.

KEYWORDS:

Colorectal cancer; Consensus clustering; Gene expression profiling; Gene set enrichment analysis; Somatic copy number alterations; Survival; lncRNA

PMID:
24954858
PMCID:
PMC5528608
DOI:
10.1016/j.molonc.2014.05.010
[Indexed for MEDLINE]
Free PMC Article

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