BackgroundADP-ribosylation factor-like protein 4 C (ARL4C) is a member of the ARF small GTP-binding protein subfamily. TheARL4Cgene is highly expressed in colorectal cancer (CRC). ARL4C protein promotes cell motility, invasion, and proliferation.MethodsWe investigated the characteristics ofARL4Cby comparing its expression at the invasion front and relationships with clinicopathological data using RNAscope, a highly sensitive RNA in situ method.ResultsIn all cases,ARL4Cexpression was observed in cancer stromal cells and cancer cells.ARL4Cexpression in cancer cells was localized at the invasion front. In cancer stromal cells,ARL4Cexpression was significantly stronger in cases with high-grade tumor budding than in cases with low-grade tumor budding (P = 0.0002). Additionally,ARL4Cexpression was significantly increased in patients with high histological grade compared with those with low histological grade (P = 0.0227). Furthermore,ARL4Cexpression was significantly stronger in lesions with the epithelial-to-mesenchymal transition (EMT) phenotype compared with the non-EMT phenotype (P = 0.0289). In CRC cells,ARL4Cexpression was significantly stronger in cells that had the EMT phenotype compared with those with a non-EMT phenotype (P = 0.0366).ARL4Cexpression was significantly higher in cancer stromal cells than in CRC cells (P < 0.0001).ConclusionOur analysis reinforces the possibility thatARL4Cexpression worsens the prognosis of patients with CRC. Further elucidation of the function ofARL4Cis desired.