In summary, we have shown that Plexin-B2 can be a prognostic factor for RMS, implying that the Plexin-B-SEMA4 signaling axis might be a potential therapeutic target for rhabdomyosarcoma; however, paradoxical effects of Plexin-B2 knockdown to increase tumor cell growth and only selectively in certain cell lines to decrease tumor cell migration raise significant concerns about therapeutic approaches to Plexin-B-SEMA4 inhibition until the factors underlying this complex biology and clinical biomarkers of response can be developed. This evidence concerns the gene SEMA3F and neoplasm.