About 3% of adult cancers are caused by renal cell carcinoma (RCC) and its pathogenesis remains elusive. Among RCC, clear cell renal cell carcinoma (ccRCC) is the predominant histological subtype. Resistance to conventional treatments leaves few treatment options for advanced ccRCC. Although the transcriptome profile of primary ccRCC has been comprehensively summarized, the transcriptome profile of metastatic ccRCC is still lacking. In this study we identified a list of metastasis-related genes and constructing a metastasis-associated prognostic gene signature. By analyzing data from GSE85258 and GSE105288 datasets, 74 genes were identified as metastasis-related genes. To construct prognostic features, we downloaded the expression data of ccRCC from the Cancer Genome Atlas (TCGA). Metastasis-associated genes were initially selected through the LASSO Cox regression analysis and 12 metastasis-related were included to construct prognostic model. Transcriptome profile, patient prognosis, and immune cell infiltration characteristics differed between low- and high-risk groups after grouping according to median risk score. Through explored the functions of differentially expressed genes (DEGs) between the two groups. Kinesin family member 23 (KIF23) was identified as a prognostic marker in ccRCC patients. Furthermore, inhibition of KIF23 expression reduced the proliferation, migration and invasion of ccRCC cells. We further demonstrated that KIF23 promote nuclear translocation of β-catenin in ccRCC cells, which provides novel insight into the functions and molecular machinery of KIF23 in ccRCC.
Keywords: Wnt/β-catenin signaling pathway; kinesin family member 23; metastasis-associated genes; prognosis signature; renal cell carcinoma.
Copyright © 2022 Wu, Song, Wu, Ge, Liu, Du, Zhang and Ma.