SOX2 and SOX12 are predictive of prognosis in patients with clear cell renal cell carcinoma.

Sex-determining region Y-box protein (SOX) genes serve an important role in cancer growth and metastasis. The present study aimed to determine the predictive ability of SOX and associated genes identified through molecular network in clear cell renal cell carcinoma (RCC). A total of 505 patients with clear cell RCC from The Cancer Genome Atlas (TCGA) cohorts were collected in this study. The expression profile of SOX and associated genes were obtained from the TCGA RNAseq database. Clinicopathological characteristics, including age, gender, tumor grade, stage, laterality disease-free-survival and overall survival (OS) were collected. Cox's proportional hazards regression model, as well as Kaplan-Meier curves were used to assess the relative factors. Selected genes of SOXs that demonstrated significant associations with OS were further validated in 192 patients from the validation cohort. In the univariate Cox regression model, SOX1, SOX2, SOX6, SOX11, SOX12, SOX13, SOX15, SOX17 and SOX30 expression were predictive in the prognosis of clear cell RCC. Following adjustment for clinical factors, SOX2 [hazard ratio (HR), 1.130; 95% confidence interval (CI), 1.002-1.275), SOX12 (HR, 1.379; 95% CI, 1.060-1.793) and SOX15 (HR, 1.245; 95% CI, 1.063-1.459) remained statistically significant. Furthermore, POU class 5 homeobox 1 (POU5F1), POU2F1 and nuclear receptor subfamily 5 group A member 1 in the gene cluster network analysis associated with SOX2 did not reduce the statistical significance when added to the multivariate analysis. The findings were extended to the Fudan University Shanghai Cancer Center cohort. The results revealed that high SOX2 and SOX12 expression were associated with poor prognosis for OS (log-rank test, all P<0.05). SOX2 and SOX12 were identified as independent prognostic factors of OS in clear cell RCC.