Xiao-Jie Wang1, Bing Zeng2, Shuangming Lin3, Min Chen4, Pan Chi5. 1. Department of Colorectal Surgery, Union Hospital, Fujian Medical University, Fuzhou, Fujian, China. 2. Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Guangzhou Medical University, Qing yuan People's Hospital, Guangdong, China. 3. Department of Gastrointestinal and Anal Surgery, Longyan First Hospital, Affiliated to Fujian Medical University, China. 4. Department of Obstetrics, Fujian Provincial Maternity and Children's Hospital, Fujian Medical University, Fuzhou, Fujian, China 912089561@qq.com. 5. Department of Colorectal Surgery, Union Hospital, Fujian Medical University, Fuzhou, Fujian, China 912089561@qq.com.
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.
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 cancerpatients. METHOD: RNA sequencing (RNA-Seq) data from 187 stage II colon cancerpatients was obtained from the TCGA data portal. We excluded cases without a sufficient amount of survival data (n=21), leaving 166 stage II colon cancerpatients 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 cancerpatients.