Clinical and RNA expression integrated signature for urothelial bladder cancer prognosis

BACKGROUND: Accumulating evidence shows that clinical factors alone are not adequate for predicting the survival of patients with urothelial bladder cancer (UBC), and many genes have been found to be associated with UBC prognosis. PURPOSE: The objective of this study is to develop a signature which integrates clinical and molecular information to predict the overall survival of UBC patients more accurate. MATERIALS AND METHODS: We integrated messenger RNA (mRNA) and microRNA (miRNA) expression profiles and the corresponding clinical data of 402 UBC patients and 19 normal controls from The Cancer Genome Atlas. Univariate Cox regression followed by a multiple testing correction and an elastic net-regulated Cox regression were adopted to identify a prognostic signature. RESULTS: We generated an integrated clinical-RNA signature which consisting of 3 clinical variables, 3 protective mRNAs, 7 risky mRNAs, 2 protective miRNAs and 1 risky miRNA. The area under the receiver operating characteristic curve of the integrated clinical-RNA signature was 0.802, larger than that of the clinical-alone signature (0.709) or the RNA-alone signature (0.726). UBC patients in the high-risk group had a significantly shorter overall survival time compared with patients in the low-risk group (clinical-RNA signature, hazard ratio = 2.441). CONCLUSIONS: Our conclusions that we have identified an integrated clinical-RNA signature that was superior to the traditional clinical-alone signature for ascertaining the overall survival prognosis of patients with UBC. These findings provide some novel genes for tumor molecular biologist to further study their functions and mechanisms in UBC tumorigenesis and malignance, and may be useful for effective clinical risk management of UBC patients.