Profiles of overall survival-related gene expression-based risk signature and their prognostic implications in clear cell renal cell carcinoma

Abstract

Abstract The present work aimed to evaluate the prognostic value of overall survival (OS)-related genes in clear cell renal cell carcinoma (ccRCC) and to develop a nomogram for clinical use. Transcriptome data from The Cancer Genome Atlas (TCGA) were collected to screen differentially expressed genes (DEGs) between ccRCC patients with OS > 5 years (149 patients) and those with <1 year (52 patients). In TCGA training set (265 patients), seven DEGs (cytochrome P450 family 3 subfamily A member 7 (CYP3A7), contactin-associated protein family member 5 (CNTNAP5), adenylate cyclase 2 (ADCY2), TOX high mobility group box family member 3 (TOX3), plasminogen (PLG), enamelin (ENAM), and collagen type VII α 1 chain (COL7A1)) were further selected to build a prognostic risk signature by the least absolute shrinkage and selection operator (LASSO) Cox regression model. Survival analysis confirmed that the OS in the high-risk group was dramatically shorter than their low-risk counterparts. Next, univariate and multivariate Cox regression revealed the seven genes-based risk score, age, and Tumor, lymph Node, and Metastasis staging system (TNM) stage were independent prognostic factors to OS, based on which a novel nomogram was constructed and validated in both TCGA validation set (265 patients) and the International Cancer Genome Consortium cohort (ICGC, 84 patients). A decent predictive performance of the nomogram was observed, the C-indices and corresponding 95% confidence intervals of TCGA training set, validation set, and ICGC cohort were 0.78 (0.74–0.82), 0.75 (0.70–0.80), and 0.70 (0.60–0.80), respectively. Moreover, the calibration plots of 3- and 5 years survival probability indicated favorable curve-fitting performance in the above three groups. In conclusion, the proposed seven genes signature-based nomogram is a promising and robust tool for predicting the OS of ccRCC, which may help tailor individualized therapeutic strategies.