Comprehensive analysis reveals KLB as a prognostic biomarker in colorectal cancer based on systematic pancancer analysis

Abstract

Background The incidence of colorectal cancer, a prevalent digestive system tumor, is increasing. Earlier research has demonstrated the significant impact of β-Klotho(KLB) on the development of metabolic disorders. Nonetheless, the function of KLB in tumors, particularly in colorectal cancer(CRC), remains underresearched. Methods By employing databases such as the TCGA, GTEx, Human Protein Atlas, UALCAN, and cBioPortal, we gathered information regarding KLB expression levels, its predictive and diagnostic importance, epigenetic characteristics, various immune and molecular subtypes, immune checkpoints, and the extent of immune infiltration. The “clusterProfiler” R package was utilized for enrichment analysis to investigate the possible role of KLB. To determine the optimal prognostic model, multivariate Cox regression and Akaike's information criterion were applied. Additionally, CCK-8 assays, colony formation assays, and cell scratch assays were employed to assess the impact of KLB on the biological activities of CRC cells. Results Pancancer studies revealed a decrease in KLB in CRC and various other cancers, but an increase in KLB in liver hepatocellular carcinoma and prostate adenocarcinoma. Consequently, reduced KLB expression correlated with a lower TNM stage and unfavorable clinical outcomes in CRC patients. The nomogram, developed considering KLB, CEA level, and TNM stage, demonstrated enhanced predictive accuracy in CRC. Analysis of immune cell infiltration revealed a correlation between reduced KLB expression and decreased infiltration of immune cells. Experiments involving CCK-8, colony formation, and cell scratch assays revealed that the increased in vitro expression of KLB suppressed the growth, movement, and infiltration of CRC cells. Conclusion The expression levels of KLB were lower in CRC tissues than in normal tissues. A notable correlation was found between its reduced expression and a grim outlook. Furthermore, KLB is crucial for the immune response of tumors and the biological actions of CRC cells. Consequently, KLB could be a potential biomarker for prognosis and a target for therapy in CRC patients.