BackgroundThe Four Jointed Box 1 (FJX1) gene has been implicated in the upregulation of various cancers, highlighting its crucial role in oncology and immunity. In order to better understand the biological function of FJX1 and identify new immunotherapy targets for cancer, we conducted a comprehensive analysis of this gene.MethodsWe analyzed the expression profiles and prognostic value of FJX1 using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Copy number alterations (CNAs), mutations, and DNA methylation were analyzed through cBioPortal. The Immune Cell Abundance Identifier (ImmuCellAI) was used to examine the correlation between FJX1 expression and immune cell infiltration. The relationship between FJX1 expression and immune-related genes and immunosuppressive pathway-related genes was analyzed using The Tumor Immune Estimation Resource version 2 (TIMER2). Tumor mutational burden (TMB) and microsatellite instability (MSI) were obtained from TCGA pan-cancer data. The effect of immunotherapy and the IC50 were assessed using IMvigor210CoreBiologies and Genomics For Drug Sensitivity in Cancer (GDSC). Finally, we evaluated the impact of FJX1 on colon cancer cell proliferation and migration throughin vitrofunctional experiments.ResultsOur study indicated that FJX1 expression was high in most cancers and was significantly associated with poor prognosis. High FJX1 expression was also linked to significant alterations in CNA, DNA methylation, TMB, and MSI. Positive correlations were found between FJX1 expression and tumor-associated macrophages (TAMs) and with immune-related genes such as TGFB1 and IL-10 and immunosuppressive pathway-related genes such as TGFB1 and WNT1. On the other hand, FJX1 expression showed a negative relationship with CD8+ T cells. Furthermore, high FJX1 expression led to reduced effectiveness of immunotherapy and drug resistance. In colon cancer cells, FJX1 knockdown was found to decrease cell proliferation and migration.ConclusionOur research findings demonstrate that FJX1 is a new prognostic factor with a significant role in tumor immunity. Our results highlight the importance of further exploring the potential of targeting FJX1 as a therapeutic strategy in cancer.