Expression And Clinical Significance Of Circadian Genes In Primary Hepatocellular Carcinoma

Objective:Hepatocellular carcinoma(HCC)is currently the third most common malignant tumor in the world,with high malignancy,morbidity and recurrence rate.The patients with HCC always show low survival rate,short survival time and poor quality of life.Therefore,the search for HCC-specific biomarkers or therapeutic targets is one of the major issues which need to be solved urgently.Circadian rhythm regulates various metabolic and physiological functions of the body.It is found that circadian rhythm is generated by circadian genes through transcription,which is a negative feedback loop.The circadian genes could interfere cell cycle,damage DNA structure,interrupt endocrine pathways,and participate in cell metabolism in many ways to promote tumors.The clinical data in the Cancer Genome Atlas(TCGA)was used to provid ideas for the diagnosis,treatment and evaluation of prognosis indicators of liver cancer and investigate the relationship between primary hepatocellular carcinoma(HCC)and the expression of circadian genes.Methods:1.The profiles were downloaded from The Cancer Genome Atlas database(TCGA),which contained 424 samples,including 374 cases of hepatoma samples and 50 cases of normal samples.2.The fifty-one circadian genes were analyzed by DE Center(|log2(FC)|>1.5?P<0.05)to obtain the differentially expressed genes(DEGs).3.The gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichments of DEGs were performed by DAVID online analyses.The protein–protein interaction(PPI)networks of the DEGs were constructed from the STRING database.Results:1.A total of 51 DEGs were identified,of which 21 genes were upregulated(P-value<0.05)and 3 genes were downregulated(P-value<0.05).2.KEGG pathway analysis showed that these DEGs were mainly involved in the Wnt signaling pathway,Hedgehog signaling pathway and Hippo signaling pathway(P-value<0.001).3.GO analysis showed that the biological functions of DEGs focused primarily on circadian rhythm,regulation of metabolic process and regulation of gene expression(P-value<0.001).The 10 most closely related genes were identified from the PPI network.Conclusions:The circadian genes participate in the development of primary hepatocellular carcinoma through the pathway of circadian rhythm and cell metabolism.Circadian gene NPAS2 may play a vital role in the development of hepatocellular carcinoma,and may also become a new biomarker for the diagnosis or prognosis of hepatocellular carcinoma,and even more likely to become a new target for liver cancer treatment.Point may also provide a new idea for future basic research and system therapy.