An Integrated miRNA-lncRNA Signature Predicts the Survival of Stage II Colon Cancer.

Abstract

OBJECTIVE:

By in silico analysis of colon cancer data from the Cancer Genome Atlas (TCGA) database, we develop a prognostic signature to improve the stratification of high-risk stage II colon cancer patients.

METHOD:

RNA sequencing (RNA-Seq) data from 187 stage II colon cancer patients was obtained from the TCGA data portal. We excluded cases without a sufficient amount of survival data (n=21), leaving 166 stage II colon cancer patients to be selected for further survival analysis. Differentially expressed lncRNAs and miRNAs were unveiled by the edgeR package of R. A comprehensive ceRNAs regulatory network was constructed using the Cytoscape. Cox regression analysis was performed to screen prognostic RNAs and develop a prognostic signature. The Multi Experiment Matrix and Gene Ontology were undertaken to assess the prognostic lncRNA MIR31HG function.

RESULTS:

The multivariate analysis indicates that 2 lncRNAs (WASIR2 and MIR31HG) and 2 miRNAs (hsa-mir-200a and hsa-mir-155) exhibited an independently significant prognostic value for stage II colon cancer. The 4 lncRNA-miRNA signatures for predicting the overall survival (OS) was constructed with the formula: Risk score=exp WASIR2*(0.213)+exp MIR31HG*(0.152)+exp hsa-mir-200a*(-0.329)+exp hsa-mir-155*(0.300). The area under the curve in the receiver operating characteristic analysis was 0.810. Kaplan-Meier survival curves confirm that the low-risk group had a low death rate, with a 5-year OS rate at 87.7%. However, the high-risk group had a low 5-year OS of 23.1% (P=0.000). The correlative genes of MIR31HG were found to be enriched in the epithelial-to-mesenchymal transition pathway, and the VEGFR3 signaling in lymphatic endothelium pathways.

CONCLUSIONS:

These findings indicate that the 4 lncRNA-miRNA prognostic signature could be a marker for survival of stage II colon cancer patients.

• Authors: Xiao-Jie Wang, Bing Zeng, Shuangming Lin, Min Chen, Pan Chi
• Journal: Annals of clinical and laboratory science (Ann Clin Lab Sci) Vol. 49 Issue 6 Pg. 730-739 (Nov 2019) ISSN: 1550-8080 [Electronic] United States
• PMID: 31882423 (Publication Type: Journal Article)
• Copyright: © 2019 by the Association of Clinical Scientists, Inc.

Chemical References

• Biomarkers, Tumor
• MIRN31 microRNA, human
• MicroRNAs
• RNA, Long Noncoding

Topics

• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics)
• Colonic Neoplasms (genetics, mortality, pathology)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Kaplan-Meier Estimate
• Male
• MicroRNAs (genetics)
• Middle Aged
• Prognosis
• Proportional Hazards Models
• RNA, Long Noncoding (genetics)