The aim of this study was to investigate the association of Von Hippel-Lindau (VHL) gene status, vascular endothelial growth factor receptor (VEGFR) or stem cell factor receptor (KIT) expression, and their relationships with characteristics and clinical outcome of advanced ccRCC.
As the identification of novel pVHL targets might provide insights into pVHL tumour suppressor activity, we performed gene expression microarray analysis in VHL-wild-type and VHL-null renal cell carcinoma (RCC) cell lines.
To develop a radiomics model with all-relevant imaging features from multiphasic computed tomography (CT) for differentiating clear cell renal cell carcinoma (ccRCC) from non-ccRCC and to investigate the possible radiogenomics link between the imaging features and a key ccRCC driver gene-the von Hippel-Lindau (VHL) gene mutation.
HIF-1α, HIF-2α and CAIX were up-regulated in 88.2% (15/17), 100% (17/17) and 88.2% (15/17) of tumors respectively and their expression is independent of VHL status. hnRNP A2/B1 and osteopontin expression was variable in CCRCCs and had no association with VHL genetic status.
Taken together, the findings of this study suggest that the protein levels of HIF2A and VEGFA in tumor tissue may serve as independent prognostic factors in ccRCC. ccRCC patients with increased intratumoral HIF2A and VEGFA protein levels, and unaltered VHL protein levels, are not likely to benefit from sunitinib treatment following nephrectomy; however, this hypothesis requires verification by large‑scale replication studies.
Our results provide a possible mechanistic explanation for the role of SENP1 in the initiation and development of ccRCC with normal VHL activity, and identifies SENP1 as a potential treatment target for the disease.