Novel VHL substrate targets SFMBT1 and ZHX2 may be important prognostic predictors in patients with ccRCC

Renal cell carcinoma is one of the most malignant cancers, with limited prognostic prediction system. The present study aimed to determine the prognostic value of novel von Hippel-Lindau (VHL) substrate targets in predicting the outcome of clear cell renal cell carcinoma (ccRCC). A total of 97 patients with ccRCC were enrolled in the present study, and the tissue microarray that was constructed using 97 ccRCC samples was used for immunohistochemical analysis. Univariate and multivariate Cox regression analyses were performed to determine the independent prognostic factors. Reverse transcription-quantitative PCR analysis demonstrated that the mRNA expression levels of scm-like with four malignant brain tumor domains (SFMBT1) and zinc fingers and homeoboxes 2 (ZHX2) were upregulated in cancer tissues compared with adjacent normal tissues. Among the 97 patients with ccRCC, SFMBT1 expression was upregulated in 61.9% (60/97), while ZHX2 expression was upregulated in 52.6% (51/97). Overall survival (OS) and disease-free survival (DFS) analyses indicated that SFMBT1 or ZHX2 alone were of limited predictive value; however, the combined expression of these two targets (high SFMBT1 and high ZHX2 expression, SHZH group) was significantly associated with OS (P=0.0350) and DFS (P=0.0434). In addition, multivariate analysis identified SHZH as an independent prognostic factor in patients with ccRCC. Taken together, these results suggest that SFMBT1 and ZHX2 act as novel substrate targets of VHL and, to the best of our knowledge, the present study was the first to provide insight on the co-expression of these two targets in representing a promising biomarker to predict the outcome of patients with ccRCC.