Immune Implication of ASF1B Gene in Hepatocellular Carcinoma

Abstract Background: Anti-silencing function 1B (ASF1B) has been demonstrated to contribute to tumorigenesis. However, its carcinogenic and immune effects in hepatocellular carcinoma (HCC) have not been reported. This study aimed to identify immune role of ASF1B in HCC.Methods: HCC datasets obtained from The Cancer Genome Atlas (TCGA) database were used to investigate the role of ASF1B gene in HCC, followed by validation using Gene Expression Omnibus (GEO) datasets and Gene Expression Profiling Interactive Analysis (GEPIA) website. CIBERSORT analysis was performed to evaluate immune cell infiltration levels. The TISIDB and cBioPortal network tool were used to seek ASF1B-associated immunomodulators and its co-expressed genes. TCGA cohort was divided into train set and test set according to the ratio of 7:3. Cox regression was used to identify ASF1B-associated prognostic immunomodulators in train set, followed by internal validation using the test set. Based on the median risk-score, HCC patients were divided into high- and low-risk group for the further survival curves and receiver operating characteristic (ROC) analysis, as well as nomogram and calibration curves analysis. Finally, the dataset collected from the GEO was adopted for external validation.Results: ASF1B was over-expressed in TCGA HCC cohort and contributed poor prognosis, which was verified in two GEO datasets (GSE14520 and GSE6764) and GEPIA, as well as Kaplan Meier Plotter network tool. The immune cell infiltration levels were found to be associated with the ASF1B copy numbers and mRNA expression. A total of 78 ASF1B-associated genes were screened out, including 7 immunoinhibitors, 21 immunostimulators and 50 tightly co-expressed genes. Finally, 5 ASF1B-associated genes (TNFSF4, TNFRSF4, KDR, MICB and CST7) were identified to be strongly related to HCC survival. Survival analysis demonstrated that the prognosis of patients in high-risk group was poor. The prognosis predict model, which was established by nomogram based on risk-score, and was validated in both TCGA test set and GEO validated datasets, exerted excellent predictive power in this study.Conclusion: Our findings showed that the ASF1B was associated with HCC immunity. The selected ASF1B-asociated immune markers could be promising biomarkers for the prognosis of HCC.