Objective:To investigate the differential expression of four-jointed box kinase 1 (FJX1) gene in colorectal cancer and its relationship with prognosis and the related mechanisms.Methods:On July 16, 2021, the transcriptome data and clinical data of colorectal cancer were downloaded from The Cancer Genome Atlas (TCGA) database to analyze the expressions of FJX1 mRNA in colorectal cancer tissues and paracancerous tissues, and the relationship between FJX1 mRNA and clinicopathological characteristics and prognosis of patients. Receiver operating characteristic (ROC) curve was drawn to evaluate the value of FJX1 mRNA in predicting the survival of patients with colorectal cancer. Cox proportional hazards model was used to evaluate whether FJX1 mRNA was an independent influencing factor for prognosis of colorectal cancer. The overall survival (OS) time and survival status of colorectal cancer patients were downloaded from the Gene Expression Omnibus (GEO) database, and the relationship between FJX1 mRNA and prognosis of patients was analyzed. The methylation data of colorectal cancer was downloaded from the University of California, Santa Cruz (UCSC xena) database to determine the degree of methylation at each site of FJX1 mRNA and the correlation between the expression of FJX1 mRNA and the degree of methylation at each site. Signaling pathways associated with FJX1 mRNA in colorectal cancer were analyzed by using the Gene Set Enrichment Analysis (GSEA) (4.1.0). The correlation between FJX1 mRNA and tumor-infiltrating immune cells was investigated by using the Tumor Immunity Evaluation Resource (TIMER) database. Spearman analysis and small molecule/drug sensitivity analysis were used to explore the correlation between FJX1 mRNA expression and drug sensitivity.Results:In the transcriptome data of 612 colorectal cancer cases in TCGA database, the expression of FJX1 mRNA in colorectal cancer tissues was higher than that in the paracancerous tissues ( P < 0.001). In 549 colorectal cancer patients with complete data, FJX1 mRNA expression was correlated with M stage ( P = 0.007), pathological stage (stage Ⅳ vs. stage Ⅰ, P = 0.016; stage Ⅳ vs. stage Ⅱ, P = 0.03; stage Ⅳ vs. stage Ⅲ, P = 0.012), but it was not correlated with age, gender, T stage and N stage (all P > 0.05). In TCGA database and GEO database, the patients were divided into high expression group and low expression group according to the median expression of FJX1 mRNA. The OS in FJX1 mRNA high expression group was worse than that in low expression group (all P<0.05). The ROC curve of FJX1 mRNA expression on the 1-, 3-, and 5-year OS rates of colorectal cancer patients was drawn by using the data in TCGA database, and the areas under the curve (AUC) were 0.595, 0.625 and 0.764, respectively. Multivariate Cox regression analysis showed that age ( HR = 1.050, 95% CI 1.028-1.073, P < 0.001), T stage ( HR = 1.787, 95% CI 1.090-2.927, P = 0.021) and high FJX1 mRNA expression ( HR = 1.160, 95% CI 1.049-1.282, P = 0.004) were independent influencing factors for poor OS in colorectal cancer. The gene set enrichment analysis found that FJX1 mRNA was related to colorectal cancer, TGF-β signaling pathway, VEGF signaling pathway, Wnt signaling pathway, etc. The expression of FJX1 mRNA in colon cancer was negatively correlated with the degree of methylation of FJX1 mRNA ( r = -0.16, P < 0.001), and the expression of FJX1 mRNA in rectal cancer was positively correlated with the degree of methylation of FJX1 mRNA ( r = 0.33, P < 0.001). The expression of FJX1 mRNA was related to the infiltration of resting memory CD4 + T cells, M0 macrophages and resting dendritic cells. FJX1 mRNA was significantly associated with the resistance of various chemotherapeutic drugs and tumor-targeted drugs such as methotrexate, 5-fluorouracil, gefitinib, etc. Conclusions:FJX1 mRNA may be a potential biomarker of colorectal cancer and is associated with the infiltration of immune cells.