Role of TFCP2/YAP transcriptional complex co-regulated protein CPE for the diagnosis of hepatocellular carcinoma

doi:10.3969/j.issn.1673-8640.2019.02.003

Abstract

Abstract:

Objective To investigate the role of transcription factor CP2（TFCP2）/Yes-associated protein（YAP） transcriptional complex co-regulated protein carboxypeptidase E（CPE） for the diagnosis of hepatocellular carcinoma（HCC）. Methods The levels of serum CPE in 147 HCC patients,42 hepatitis B patients,29 gastric cancer patients and 100 healthy subjects（healthy control group） were determined by enzyme-linked immunosorbent assay. Real-time fluorescence quantitation polymerase chain reaction（PCR） was used to determine the expression of CPE mRNA. Western blotting was used to determine the expression of CPE,TFCP2 and YAP. The dual-luciferase reporter test was used to determine the activity of CPE promoter. The correlations between CPE and other indicators such as alpha-fetoprotein（AFP）,alanine aminotransferase（ALT） and aspartate aminotransferase（AST） were analyzed using Spearman correlation analysis. Receiver operating characteristic（ROC） curve was used to compare the efficiency of CPE and AFP for the diagnosis of HCC. Results The overexpression of YAP or TFCP2 stimulated the expression of CPE mRNA and protein,and the overexpression of YAP and TFCP2 stimulated the expression ofCPE mRNA and protein. The knockdown of YAP or TFCP2 inhibited the expression of CPE mRNA and protein,and the knockdown of YAP and TFCP2 inhibited the expression of CPE mRNA and protein. A TFCP2-binding-motif was existed in CPE promoter region. After mutation,TFCP2 and YAP lost the regulation function on CPE promoter. The level of serum CPE was higher in HCC group than those in healthy control,hepatitis B and gastric cancer groups（P<0.01）,and there was no statistical significance among healthy control,hepatitis B and gastric cancer groups（P>0.05）. The level of serum CPE was positively correlated with the levels of AFP,ALT and AST（r=0.644,0.454 and 0.351,P=0.000,0.000 and 0.001,respectively）. The area under ROC curve（AUC） of CPE for the diagnosis of HCC was 0.937,which is better than that of AFP（0.679）. Conclusions CPE plays a role in the diagnosis of HCC,and CPE may be a diagnostic biomarker for HCC.

Key words: Carboxypeptidase E, Transcription factor CP2, Yes-associated protein, Hepatocellular carcinoma

CLC Number:

Q556

FANG Zixiang, ZHANG Xiao, CHEN Yan, WU Qi, ZHU Guoqing, LIU Ya, WANG Jiayi, SUN Fenyong, YU Lei. Role of TFCP2/YAP transcriptional complex co-regulated protein CPE for the diagnosis of hepatocellular carcinoma[J]. Laboratory Medicine, 2019, 34(2): 103-109.

Figures/Tables 5

References 28

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