Proteomic analysis and validation of DNA repair regulation in the process of hepatocellular carcinoma recurrence

Kai Chang; Yanyan Wang; Zhongyong Jiang; Wei Sun; Chenxia Liu; Wanlin NA; Hongxuan XU; Jing Xie; Yuan Liu; Min Chen

Return

Proteomic analysis and validation of DNA repair regulation in the process of hepatocellular carcinoma recurrence

VernacularTitle:肝细胞癌复发进程中DNA修复调节的蛋白质组学分析及验证
Author: Kai CHANG ¹ ; Yanyan WANG ¹ ; Zhongyong JIANG ² ; Wei SUN ¹ ; Chenxia LIU ³ ; Wanlin NA ¹ ; Hongxuan XU ⁴ ; Jing XIE ¹ ; Yuan LIU ¹ ; Min CHEN ¹
Author Information

1. Department of Clinical Laboratory， The General Hospital of Western Theater Command， Chengdu 610083， China
2. Department of Medical Laboratory， Affiliated Cancer Hospital of Chengdu Medical College， Chengdu Seventh People’s Hospital， Chengdu 610041， China
3. Institute of Microbiology， Sichuan Provincial Center for Disease Control and Prevention， Chengdu 610041， China
4. Biology Teaching and Research Group， Chengdu Experimental Foreign Languages School， Chengdu 611134， China
Publication Type:Journal Article
Keywords: Carcinoma， Hepatocellular; Neoplasm Recurrence， Local; DNA Repair; Proteomics
From: Journal of Clinical Hepatology 2024;40(2):319-326
CountryChina
Language:Chinese
Abstract: ObjectiveTo investigate the role and mechanism of DNA repair regulation in the process of hepatocellular carcinoma （HCC） recurrence. MethodsHCC 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. ResultsFor 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）. ConclusionThere are significant reductions or deletions of multiple complex protein components in the process of DNA repair during HCC recurrence.