Interferon-stimulating gene 15(ISG15),an ubiquitin-like molecule belonging to the superfamily of ubiquitin-like proteins,is highly expressed in various malignant tumors and induced by type Ⅰ interferon.How-ever,its specific regulatory mechanism remains unclear.Numerous studies have demonstrated its close association with tumorigenesis and development.In this study,we provide a comprehensive review on the role of ISG15 protein in hepatocellular carcinoma,esophageal carcinoma,gastric carcinoma,colorectal carcinoma,and other cancers.Our aim is to identify new therapeutic targets for gastrointestinal malignancies and improve prognostic assessment.

Interferon-stimulating gene 15(ISG15),an ubiquitin-like molecule belonging to the superfamily of ubiquitin-like proteins,is highly expressed in various malignant tumors and induced by type Ⅰ interferon.How-ever,its specific regulatory mechanism remains unclear.Numerous studies have demonstrated its close association with tumorigenesis and development.In this study,we provide a comprehensive review on the role of ISG15 protein in hepatocellular carcinoma,esophageal carcinoma,gastric carcinoma,colorectal carcinoma,and other cancers.Our aim is to identify new therapeutic targets for gastrointestinal malignancies and improve prognostic assessment.