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

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 < 1 year (52 patients). In TCGA training set (265 patients), seven DEGs (CYP3A7, CNTNAP5, ADCY2, TOX3, PLG, ENAM, and COL7A1) were further selected to build a prognostic risk signature by the least absolute shrinkage and selection operator 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 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 3 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.

M2‐polarization‐related CNTNAP1 gene might be a novel immunotherapeutic target and biomarker for clear cell renal cell carcinoma

“…For instance, the aberrant expression of CNTNAP5 has been reported to be related to ccRCC prognosis. 22 CNTNAP2, as a cell adhesion molecule, has been reported to be methylated or deleted in a variety of cancers, for example, glioma, 23 myeloid leukemia, 24 and pancreatic ductal adenocarcinoma. 25 CNTNAP2 antibodies have strong and specific clinical associations and are highly immunotherapy responsive in glioma.…”

“…The neurexin superfamily also included CNTNAP2‐5, which had been implicated in cancers. For instance, the aberrant expression of CNTNAP5 has been reported to be related to ccRCC prognosis 22 . CNTNAP2, as a cell adhesion molecule, has been reported to be methylated or deleted in a variety of cancers, for example, glioma, 23 myeloid leukemia, 24 and pancreatic ductal adenocarcinoma 25 .…”