Comprehensive Analysis of the Expression of IGFBPs and its Correlation with Prognosis and Immune in Endometrial Cancer

Abstract

Abstract Endometrial cancer (EC) is one of the most common malignant tumors of the female reproductive tract. Insulin-like growth factor-binding proteins (IGFBPs) as regulators of IGF signaling in cancer are of increasing interest. However, the role of the IGFBP family in EC has not been fully explored. The expression of IGFBPs and their association with clinical prognosis, biological function, mutation status, and immune infiltration in EC patients were investigated using the TCGA, STRING, cBioPortal, TIMER and TCIA databases. The protein levels of the IGFBP family in collected patient samples were further identified by immunohistochemical methods. In patients with EC, IGFBP2 was significantly upregulated, while other IGFBPs were downregulated. The expression levels of IGFBP4 and IGFBP7 in EC decreased with increasing tumor grade and low expression of IGFBP4 was correlated with poor overall survival. The co-expression network and enrichment analysis results showed that IGFBP4 was related to microtubule-based movement, collagen-containing extracellular matrix, and vascular smooth muscle contraction. Moreover, IGFBP2/3/4/7 expression was correlated with tumor mutation burden and the levels of tumor-infiltrating immune cells in EC, and IGFBP7 in particular was significantly associated with immunotherapy response. This study revealed the expression of the IGFBP family in EC patients and showed that IGFBP4 could be a valuable prognostic indicator and that IGFBP7 may be a potential immunotherapeutic target for EC.