Expression And Significance Of ASF1B In Hepatocellular Carcinoma

Background and Objective: Liver cancer ranks second in the new cases of male malignant tumors in our country,and 85-90% of which are hepatocellular carcinoma(HCC).Currently,the main treatment methods for HCC include medical chemotherapy,radiotherapy,surgical therapy,targeted therapy,and immunotherapy,etc.However,most HCC patients are diagnosed at an advanced stage,with high mortality and poor prognosis.One of the most important features of malignant tumors is metastasis,which is also the cause of poor prognosis.Therefore,it is necessary to further study the molecular mechanism of HCC metastasis and search for new molecular targets,so as to provide basic research for the generation of new molecular targeted drugs in the future.Anti-silence function 1(ASF1)is a companion of histone H3-H4.ASF1 is crucial to the S-phase of cell proliferation and is involved in gene replication,transcription and DNA repair.ASF1 contains two para-homologous ASF1 A and ASF1 B,which have different functions.ASF1 A is mainly involved in DNA repair and cell silencing,and promotes cell aging.ASF1 B is mainly involved in cell cycle progression and cell proliferation.Currently,it has been reported that ASF1 B is upregulated in cervical cancer,breast cancer,gastric cancer,liver cancer and other malignant tumor tissues compared with paracancer tissues,promoting tumor proliferation and metastasis.This study confirmed the up-regulated expression of ASF1 B in hepatocellular carcinoma through cell experiments,and further demonstrated the prognostic relationship between ASF1 B and patients by collecting clinical data of88 patients with HCC.Methods: We searched The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus database(GEO)to analyze the expression of ASF1 B in HCC and paracancer tissues,as well as its correlation with prognosis.Western Blot(WB),real-time quantitative PCR(q RT-PCR),and immunohistochemistry(IHC)were used to detect the expression of ASF1 B in cancer and paracancerous tissues of HCC patients.Pathological samples of 88 HCC patients were collected for q RT-PCR to detect the expression level of ASF1 B,and the clinical information was collected for prognostic analysis.Results: TCGA and GEO database analysis showed that the expression of ASF1 B in tumor tissues of HCC patients was significantly higher than that in adjacent normal tissues,and patients with high expression of ASF1 B had shorter disease-free survival and worse overall survival.It is suggested that the up-regulated expression of ASF1 B may be involved in the occurrence and development of HCC.Further analysis of the expression of ASF1 B in each pathological stage of HCC in the TCGA database showed that the expression level of ASF1 B in patients with pathological stage II was higher than that in patients with stage I,and the expression level was the highest in patients with stage III HCC.A proportional hazards regression model(Cox model)was established for univariate survival analysis of ASF1 B and other HCC related clinical data in the TCGA database,and the results showed that ASF1 B expression could be an independent prognostic factor for HCC patients.The results of WB and q RT-PCR showed that the expression level of ASFIB in HCC cell lines HEP G2 and HEP3 B was higher than that in Huh7 and 8024 cell lines.IHC results showed that ASFIB expression in HCC patients was higher than that in paracancerous tissues.The analysis of pathological specimens and clinical data collected from 88 HCC patients showed that the high expression of ASF1 B was significantly correlated with the poor prognosis of patients.COX univariate and multivariate regression analysis suggested that the expression of ASF1 B could be used as an independent prognostic factor of HCC patients.Kaplan-Meier analysis showed that the overall survival of patients with high expression of ASF1 B was significantly lower than that of patients with low expression.Based on the current analysis results,we believe that ASF1 B may be an important tumor driver gene,which plays an important role in the occurrence and development of HCC.Conclusion: The expression of ASF1 B is up-regulated in HCC patients,which is significantly correlated with poor prognosis.It is an independent prognostic factor for patients with HCC,it can be used as a potential molecular marker for hepatocellular carcinoma.To provide a certain basis for the generation of new molecular targeted drugs in hepatocellular carcinoma patients in the future.