Expression Of CGAS In Hepatocelluar Carcinoma Tissue And Its Biological Function On Hepatocelluar Carcinoma Cells

BackgroundLiver cancer is one of the most common malignant tumors with high morbidity and mortality.Hepatocellular carcinoma(HCC)is the most common type of liver cancer.Recent years,a number of early diagnosis and available treatment strategies have been applied in clinical work.However,the prognosis of HCC remains poor due to high early metastasis and recurrence rate.Therefore,it is urgent to explore the potential molecular mechanism involved in the development of HCC,which will help clinicians identifying novel and effective therapeutic targets and thus achieve clinical transformation to improve early diagnosis and prognosis of HCC patients.Cyclic guanylate-adenylate synthetase(cGAS)could catalyze the second messenger cGAMP by recognizing exogenous double-stranded DNA and the endogenous dsDNA.cGAMP can bind and activate the interferon-stimulating protein STING,and followed by the activation of type I interferon and immune factor-mediated immune response.Previous publications have identified that cGAS-STING signaling pathway plays an important role in tumor progression.For instance,aberrant activation of the cGAS-STING signaling pathway was reported involved in the initiation and progression of skin tumors,breast cancer,and colorectal cancer.Notably,recent studies demonstrated that cGAS could inhibit DNA homologous recombination repair and promote tumorigenesis,which indicated that cGAS plays an important role in tumorigenesis and immune process.However,its potential molecular mechanism in the progression of HCC remains unknown.ObjectiveThis study was aim to analyze the expression status of cGAS in pan-cancer tissues especially in HCC based on public database and TMA analysis.The clinical significance and biological function of cGAS in HCC was further explored.Methods1.The mRNA expression profiling of cGAS in common human tumors were analyzed using TCGA and GTEx database.The protein expression level of cGAS in pan-cancer tissues and corresponding normal tissues was analyzed through TMA analysis.2.The expression status and clinical significance of cGAS in HCC were explored based on TCGA-LIHC dataset.The protein expression level of cGAS was further validated by HCC TMA cohort using IHC and western blot.3.Using RNAi technology to explore the biologic effect of cGAS on HCC cells.4.Bioinformatics analysis was performed to predict the underlying mechanism which cGAS involved in HCC.5.Statistical analysis was performed using R Studio,GraphPad Prism 8.0 and SPSS 23.0 software.All data are expressed in Mean ± SD.Kaplan-Meier curves and log-rank tests were used to analyze the relationship between cGAS expression and HCC patients.Comparison between two groups was conducted using Students’t-tests.P value less than 0.05 was considered as statistical significance.α=0.05 as the inspection level.Results1.The expression level of cGAS mRNA is significantly different in many tumors.2.Both the mRNA and protein expression level of cGAS were significantly higher in HCC tissues than that in adjacent normal tissues.Furthermore,HCC patients with high cGAS expression had poor prognosis than that of HCC patients with low cGAS expression.3.Silencing cGAS inhibited the proliferation ability of HCC cell lines;Silencing cGAS significantly reduced migration and invasion ability of HCC cell lines.4.Bioinformatics analysis showed that cGAS expression is closely related to DNA repair,immune inflammation-related pathways and immune infiltration in HCC.Conclusion1.cGAS has significantly abnormal expression profiles in common human tumors.2.cGAS is significantly overexpressed in HCC tissues.And the high expression of cGAS is significantly related to the malignant phenotype and poor prognosis of patients with HCC.cGAS might be a novel promising early diagnosis biomarker and therapeutic target for HCC.3.High expression of cGAS promotes the proliferation and migration of HCC cell lines.4.cGAS may be involved in the immune inflammatory response and DNA repair process of HCC.