The Integrative Analysis of Thrombospondin Family Genes in Pan-Cancer Reveals that THBS2 Facilitates Gastrointestinal Cancer Metastasis

Abstract

Recent cancer studies have found that the thrombospondin (THBS) family, including THBS1, THBS2, THBS3, THBS4, and THBS5, play vital roles in the development and progression of human cancers. However, their relationships with tumor stage, prognosis, and tumor immunity in pan-cancer have not been systematically reported. In the present study, we employed versatile public databases to assess the expression and mutations of different THBSs in pan-cancer and performed functional experiments to analyze the roles of THBS2 in gastrointestinal cancer metastasis. Our findings indicate that THBS genes are frequently mutated in various cancers and the dysregulation of THBS family members is associated with the progression of some cancers such as gastric cancer, colon cancer, and lung cancer. Further analyses indicate that THBS genes are associated with cancer hallmarks such as cell cycle and epithelial-mesenchymal transition (EMT). Importantly, thrombospondins, especially THBS1 and THBS2, are correlated with the immune cell infiltration level in gastrointestinal cancers. Our experiments further verified that THBS2 participates in tumor metastasis by enhancing EMT. Therefore, the overall analyses reveal that THBSs might offer us potential chances for tumor diagnosis and therapy.