Coding RNA Expression Profile Of The Invasive Margin Was Associated With The Prognosis Of Hepatocellular Carcinoma

Objective: Coding RNA plays an important role which lead to tumors.It is of significance to study mRNA that is abnormally expressed in the invasive border of hepatocellular carcinoma(HCC),which may be associated with tumor biological behavior and patient prognosis.Method: We performed differential expression analysis of the data stored in the GEO database,and verified the analysis results using heatmap and hierarchical clustering.Venn analysis screened DEGs that were up-regulated and down-regulated simultaneously at the HCC center and the invasive border.Functional,pathway-enriched,and protein-interaction analyses were performed based on these DEGs.The potentially important DEGs were validated in the TCGA database,and the correlations between these DEG expression values and patient survival time as well as the HCC stage were evaluated.Finally,we validated CDC45 with the characteristic high expression on the invasive margin in clinical samples and Huh7,HCCLM3 and L02 cell lines.Result: We screened 1981 DEGs at the HCC center and 382 DEGs at the invasive border.301 DEGs showed the same up-regulation/ down-regulation tendency at the invasive border and at the HCC center,and the expression level of CDC45 at the invasive border was higher than that of the HCC center.These 301 DEGs are mainly enriched in mitosis,signal transduction,cell cycle,p53 pathway and other signaling pathways involved in cancers.Potentially key mRNAs were verified by data stored in the TCGA database,demonstrating that CDC45,FAM83 D,AURKB,TPX2,and CHEK1 expression are up-regulated in HCC,and the up-regulation of these DEGs was associated with reduced overall survival(OS)and progressive AJCC TNM staging.Finally,the abnormally high expression level of CDC45 at the invasive border(higher than the HCC center)was verified in clinical samples,and the expression level of CDC45 was also elevated in the liver cancer cell lines Huh7 and HCCLM3.Conclusion: The study illustrated that the differentially expressed mRNA in HCC has spatial distribution differences in tumor tissues.These differences could predict specific biological functions,reflect the survival time,and correlate with tumor stage of patients to some extent.This study may provide new perspectives for postoperative management and precision treatment of HCC.