SEMA3G functions as a novel prognostic biomarker associated with Wnt pathway in clear cell renal cell carcinoma.

Renal cell cancer (RCC) is one of the most common cancer, and the incidence of clear cell renal cell cancer rank at the first among multiple subtypes of RCC. Tumor heterogeneity and limited therapies expedite researches and studies on prognostic biomarkers and molecular mechanism. SEMA3G mediates various bimolecular processes but few studies have assessed the influence of SEMA3G on ccRCC. The expression of SEMA3G at mRNA level in ccRCC was analyzed using 4 TCGA datasets. The expression at protein level was verified by immunohistochemistry and western blot. Biological pathway was explored by GSEA and western blot. At both mRNA and protein level, SEMA3G expressed significantly lower in ccRCC tissues compared with normal renal tissues, and the expression was highly associated with clinical stage and pathological grade. Low expression of SEMA3G indicated a poorer overall survival and disease specific survival. Transwell and wound-healing assays showed that overexpressed SEMA3G inhibited the cell motility of renal cancer cells. Upregulated SEMA3G suppressed the invasion and proliferation of both 769-P and 786-O cells. Wnt signaling pathway was tested to work in the interfering of SEMA3G on tumorigenesis and progression of ccRCC. The results provide novel insight into the role of SEMA3G in ccRCC, suggesting the prognostic value and potential suppressor role of SEMA3G.