F-Box and Leucine-Rich Repeat Protein 7 Is a Prognostic Biomarker and Is Correlated with the Immunosuppressive Microenvironment in Colorectal Cancer.

Abstract

Background: Colorectal cancer (CRC) is a common malignancy of the digestive system, but its specific mechanisms of occurrence and development remain incompletely understood. F-Box and leucine-rich repeat protein 7 (FBXL7) is a subunit of the Skp-cullin-F-box ubiquitin ligase, involved in cell cycle regulation, endothelial cell damage, and inflammatory immunological responses. However, the role of FBXL7 in CRC remains unknown. In this study, we investigated the clinical significance and potential mechanism of FBXL7 expression in CRC progression. Methods: We utilized data from The Cancer Genome Atlas (TCGA) and the University of California Santa Cruz Xena (UCSC Xena) database for bioinformatic analyses. Clinical CRC samples were used to confirm FBXL7 expression. Gene set enrichment analysis (GSEA) and various databases, such as TCGA, UCSC Xena, cBioPortal, University of ALabama at Birmingham CANcer data analysis portal, MethSurv, Tumor Immune Estimation Resource (TIMER), TIMER2.0, Tumor-Immune System Interaction Database, and Tumor Immune Dysfunction and Exclusion Database (TIDB), were used to investigate the role of FBXL7 in CRC. Statistical analysis was performed using R (v.3.6.3) or GraphPad Prism 8.0. Results: Our findings revealed the predictive significance of FBXL7 in CRC patients. FBXL7 expression was associated with tumor stage, lymph node stage, pathological stage, perineural invasion, and lymphatic invasion. GSEA analysis identified associations between FBXL7 and extracellular matrix organization, as well as immune-related pathways. Immunological analysis revealed a correlation between high FBXL7 expression and the development of an immunosuppressive microenvironment. Conclusion: Identifying FBXL7 as a novel biomarker for CRC could shed light on the promotion of CRC development by the immune environment.