An Integrative Analysis Framework for Identifying the Prognostic Markers from Multidimensional RNA Data of Clear Cell Renal Cell Carcinoma

The altered regulatory status of long noncoding RNA (lncRNA), miRNA, and mRNA and their interactions play critical roles in tumor proliferation, metastasis, and progression, which ultimately influence cancer prognosis. However, there are limited studies of comprehensive identification of prognostic biomarkers from combined data sets of the three RNA types in the highly metastatic clear cell renal cell carcinoma (ccRCC). The current study employed an integrative analysis framework of functional genomics approaches and machine learning methods to the lncRNA, miRNA, and mRNA data and identified 16 RNAs (3 lncRNAs, 6 miRNAs, and 7 mRNAs) of prognostic value, with 9 of them novel. A 16 RNA-based score was established for prognosis prediction of ccRCC with significance (P < 0.0001). The area under the curve for the score model was 0.868 to 0.870 in the training cohort and 0.714 to 0.778 in the validation cohort. Construction of the lncRNA-miRNA-mRNA interaction network showed that the downstream mRNAs and upstream lncRNAs in the network initiated from the miRNA or lncRNA markers exhibit significant enrichment in functional classifications associated with cancer metastasis, proliferation, progression, or prognosis. The functional analysis provided clear support for the role of the RNA biomarkers in predicting cancer prognosis. This study provides promising biomarkers for predicting prognosis of ccRCC using multidimensional RNA data, and these findings are expected to facilitate potential clinical applications of the biomarkers.