摘要
Abstract
Objective:Dual-specificity tyrosine phosphorylation-regulated kinases(CDC-like kinases,CLKs)are a type of dual-specificity protein kinase involved in various pathological and physiological processes including neurological diseases,metabolic abnormalities,and tumors.Among them,CDC-like kinases 3(CLK3)is involved in the development of various cancers,such as hepatocellular carcinoma and breast cancer.However,its expression and clinical significance in colorectal cancer have not been reported.This study aims to explore the expression and clinical significance of CLK3 in colorectal cancer through mining online tumor databases.
Methods:The differential expression of CLK3 between tumor tissues and normal tissues in colorectal cancer was analyzed by the Gene Expression Profiling Interactive Analysis 2(GEPIA2)database and the GEO2R tool.After obtaining the differential expression results,the University of Alabama at Birmingham Cancer Data Analysis Portal(UALCN)database was used for Kaplan-Meier survival analysis on the groups with differential expression of CLK3.The LinkedOmics database was used for co-expression analysis of CLK3,and the top 50 positively and negatively correlated genes were selected.These 100 genes were then subjected to gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.CLK3 was also analyzed for immune-related characteristics using the TIMER2.0 database.At the tissue expression level,the Human Protein Atlas(HPA)database was used to investigate the immunohistochemical specimens of CLK3 in colorectal cancer and normal intestinal tissues,analyzing its expression differences.
Results:In the UALCN database,CLK3 was underexpressed in colon cancer tissues compared to normal tissues(P<0.01),while there was no significant difference in expression in rectal cancer tissues(P>0.05).The expression level of CLK3 was significantly associated with the prognosis of colorectal cancer patients(P<0.05),indicating that higher expression of CLK3 was associated with poor prognosis.GO and KEGG pathway enrichment results showed that genes co-expressed with CLK3 were involved in antigen peptide presentation,substance metabolism synthesis processes,enzyme reactions in transcription regulation processes,gamma interferon-mediated signaling pathways,Wnt signaling pathways,and intestinal immune inflammation processes.Correlation analysis showed that in colon cancer,the expression of CLK3 was associated with mutations in the BRAF,HERS,NTRK1,and PIK3CA genes,in rectal cancer,its expression was associated with BRAF and PIK3CA genes mutations.Further analysis of immune infiltration showed that in colon cancer,the expression level of CLK3 was positively correlated with the infiltration levels of CD8+T cells,CD4+T cells,neutrophils,and dendritic cells(all P<0.05),in rectal cancer,it was positively correlated with the infiltration levels of CD4+T cells,macrophages,neutrophils,and dendritic cells(all P<0.05).In immunohistochemical staining slides,the protein expression levels of CLK3 in both colon and rectal cancer were lower than those in normal colon tissues(all P<0.05).
Conclusion:CLK3 exhibits differential expression in colorectal cancer and is an indicator of survival prognosis.It has the potential to become one of the effective targets for prognosis assessment and clinical treatment of colorectal cancer.关键词
CDC样激酶3/结直肠癌/预后基因/矛盾表达Key words
CDC-like kinases 3/colorectal cancer/prognostic gene/paradoxical expression
