Proteomic analysis and validation of DNA repair regulation in the process of hepatocellular carcinoma recurrence
Objective To investigate the role and mechanism of DNA repair regulation in the process of hepatocellular carcinoma(HCC)recurrence.Methods HCC tissue samples were collected from the patients with recurrence within two years or the patients with a good prognosis after 5 years,and the Tandem Mass Tag-labeled quantification proteomic study was used to analyze the differentially expressed proteins enriched in the four pathways of DNA replication,mismatch repair,base excision repair,and nucleotide excision repair,and the regulatory pathways and targets that play a key role in the process of HCC recurrence were analyzed to predict the possible regulatory mechanisms.The independent samples t-test was used for comparison of continuous data between two groups;a one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results For the eukaryotic replication complex pathway,there were significant reductions in the protein expression levels of MCM2(P=0.018),MCM3(P=0.047),MCM4(P=0.014),MCM5(P=0.008),MCM6(P=0.006),MCM7(P=0.007),PCNA(P=0.019),RFC4(P=0.002),RFC5(P<0.001),and LIG1(P=0.042);for the nucleotide excision repair pathway,there were significant reductions in the protein expression levels of PCNA(P=0.019),RFC4(P=0.002),RFC5(P<0.001),and LIG1(P=0.042);for the base excision repair pathway,there were significant reductions in the protein expression levels of PCNA(P=0.019)and LIG1(P=0.042)in the HCC recurrence group;for the mismatch repair pathway,there were significant reductions in the protein expression levels of MSH2(P=0.026),MSH6(P= 0.006),RFC4(P=0.002),RFC5(P<0.001),PCNA(P=0.019),and LIG1(P=0.042)in recurrent HCC tissue.The differentially expressed proteins were involved in the important components of MCM complex,DNA polymerase complex,ligase LIG1,long patch base shear repair complex(long patch BER),and DNA mismatch repair protein complex.The clinical sample validation analysis of important differentially expressed proteins regulated by DNA repair showed that except for MCM6 with a trend of reduction,the recurrence group also had significant reductions in the relative protein expression levels of MCM5(P=0.008),MCM7(P=0.007),RCF4(P=0.002),RCF5(P<0.001),and MSH6(P=0.006).Conclusion There are significant reductions or deletions of multiple complex protein components in the process of DNA repair during HCC recurrence.
四川省自然科学基金四川省中医药管理局专项课题西部战区总医院应用基础研究项目西部战区总医院应用基础研究项目西部战区总医院星火青年创新人才工程Spark Young Innovative Talent Project of General Hospital of Western Theater Command
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维普
