Comprehensive assessment gene signatures for clear cell renal cell carcinoma prognosis

Abstract

There are many prognostic gene signature models in clear cell renal cell carcinoma (ccRCC). However, different results from various methods and samples are hard to contribute to clinical practice. It is necessary to develop a robust gene signature for improving clinical practice in ccRCC. A method was proposed to integrate least absolute shrinkage and selection operator and multiple Cox regression to obtain mRNA and microRNA signature from the cancer genomic atlas database for predicting prognosis of ccRCC. The gene signature model consisted by 5 mRNAs and 1 microRNA was identified. Prognosis index (PI) model was constructed from RNA expression and median value of PI is used to classified patients into high- and low-risk groups. The results showed that high-risk patients showed significantly decrease survival comparison with low-risk groups [hazard ratio (HR) =7.13, 95% confidence interval = 3.71–13.70, P < .001]. As the gene signature was mainly consisted by mRNA, the validation data can use transcriptomic data to verify. For comparison of the performance with previous works, other gene signature models and 4 datasets of ccRCC were retrieved from publications and public database. For estimating PI in each model, 3 indicators including HR, concordance index, and the area under the curve of receiver operating characteristic for 3 years were calculated across 4 independent datasets. The comparison results showed that the integrative model from our study was more robust than other models via comprehensive analysis. These findings provide some genes for further study their functions and mechanisms in ccRCC tumorigenesis and malignance, and may be useful for effective clinical decision making of ccRCC patients.