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.
Highlights
As one of the most common urinary malignancies, renal cell carcinoma (RCC) poses a hidden threat to public health and accounts for approximately 2–3% of adult tumors [1]
By comparing 149 samples with overall survival (OS) > 5 years with 52 samples with OS < 1 year, 614 differentially expressed gene (DEG) with criteria set as false discovery rate (FDR) < 0.05 were identified
The top 15 significantly enriched Gene Oncology (GO) terms were gathered in Figure 2A and Supplementary Table S1, indicating that DEGs associated with pivotal terms such as the ‘oxidation-reduction process’ (GO category: biological process), ‘cytoplasm’ (GO category: cellular component), and ‘protein binding’ (GO category: molecular function)
Summary
As one of the most common urinary malignancies, renal cell carcinoma (RCC) poses a hidden threat to public health and accounts for approximately 2–3% of adult tumors [1]. The morphologic and genetic heterogeneity of ccRCC was discussed in numerous previous studies [7,8]. Such reports suggested that the prevalent prognostic tools for ccRCC, which were based mainly on pathological and clinical features, had unsatisfactory predictive power. Typical tools of this kind included the TNM staging system, necrosis score, and the University of California Integrated Staging System (UISS) [9,10,11]
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