FBXL22, a circadian-regulated immune biomarker with pan-cancer prognostic value and therapeutic potential in prostate cancer.

F-box and leucine-rich repeat protein 22 (FBXL22) has been implicated in breast and prostate cancer types; however, comprehensive pan-cancer analyses and detailed investigations of its role in cancer development are still needed. To address this, the present study used The Cancer Genome Atlas, Genotype-Tissue Expression, University of ALabama at Birmingham CANcer data analysis Portal, Kaplan-Meier-Plotter and cBioPortal databases to analyze the correlation between FBXL22 expression and prognosis, gene mutations, DNA methylation, immune cell infiltration and immune-related gene regulation in several types of cancer. The findings of the present study demonstrated that FBXL22 was predominantly downregulated in several cancer types and may serve as a prognostic and diagnostic marker in certain cancer types, particularly prostate cancer. Strong correlations between FBXL22 expression and immune checkpoint genes were observed, which suggests a role in the tumor immune microenvironment. Additionally, FBXL22 expression was associated with infiltration of cancer-associated fibroblasts and endothelial cells, which may affect immunotherapy outcomes. Mechanistically, FBXL22 was involved in circadian rhythm regulation, ubiquitin-mediated proteolysis, focal adhesion signaling and cGMP-protein kinase G signaling. In prostate cancer, FBXL22 upregulation suppressed cell viability, invasion and metastasis, while promoting apoptosis, potentially through modulation of the polo-like kinase 1 pathway. To the best of our knowledge, the present study provides the first comprehensive pan-cancer analysis of FBXL22, which highlights its potential as an immune biomarker and therapeutic target for multiple cancer types with implications for precision medicine.