BTN3A1 Is Highly Expressed And Associated With Immune Cell Infiltration In Hepatocellular Carcinoma

Background: Hepatocellular carcinoma(HCC)is one of the malignant tumors that seriously threaten human health.Currently,the main clinical treatment methods for HCC include surgical resection,hepatic arterial chemoembolization(TACE),radiofrequency ablation and liver transplantation.The incidence of HCC is high in China.Many patients have entered the terminal stage of the disease when they are diagnosed,resulting in poor treatment effect,high mortality,high recurrence rate.Even if radiotherapy and chemotherapy are taken,the treatment effect is still limited.In recent years,immunotherapy has become a hot topic in basic and clinical research of malignant tumors.Tumor immunotherapy is a new therapeutic method,which can enhance the anti-tumor immunity of tumor microenvironment by stimulating the immune function of the body,so as to kill tumor cells.However,many HCC patients do not benefit from immunotherapy,but instead suffer from complications such as ImmuneRelated Adverse Event(IRAE),so it is particularly important to dig into the potential mechanism of molecules affecting the immune microenvironment of HCC.The BTN3 A family,also known as CD277,is a subfamily of lactophilic proteins that includes BTN3A1,BTN3A2,and BTN3A3.The BTN3 A family regulates the antigen-specificαβ-T cell response and plays a key role in regulating γδ-T cell function.Anti-BTN3A1 antibody transform BTN3A1 from an immunosuppressant to an immunostimulator molecule,thereby dynamically stimulating anti-tumor immunity driven by coordinatingαβ and γδ-T cells,thereby preventing the progression of ovarian cancer.Bioinformatics mining technology is a popular research method,which can analyze high-throughput sequencing data and corresponding clinical information in public databases,mine potential tumor markers,and predict their possible biological functions.In this study,the expression of BTN3A1 in HCC and its relationship with immune infiltration of HCC were explored through bioinformatics mining technology,in order to obtain new potential therapeutic targets,so as to provide new ideas for the treatment of HCC.Methods: The expression levels of BTN3A1 in pan-cancer were analyzed through the TIMER(Tumor Immune Estimation Resource)database.Then,the unified and standardized pan-cancer data set was downloaded from the UCSC(University of California Santa Cruz)database:TCGA TARGET GTEx(PANCAN,N=19131,G=60499)once again verified the expression data of BTN3A1 gene in each sample.Subsequently,R language was used to analyze the correlation between BTN3A1 and immune cells in the pan-cancer data set.And then,we determined the expression differences of BTN3A1 m RNA and protein levels in HCC tissues and normal tissues adjacent to cancer by Western blot and quantitative real time polymerase chain reaction(q RT-PCR).Gene set enrichment analysis GO,KEGG and GSEA were employed to explore the potential biological function and signaling pathway of BTN3A1.TIMER(Tumor Immune Estimation Resource)database was utilized to analyze the correlation between the expression of BTN3A1 in HCC,immune cell infiltration,and the expression level of immune cellular biomarkers.Results: The expression of BTN3A1 varies in different tumors,among which,it is significantly up-regulated in renal cell carcinoma,hepatocellular carcinoma,bile duct cell carcinoma,esophageal carcinoma,and significantly down-regulated in breast invasive carcinoma,renal chromaphrodisic cell carcinoma,endometrial carcinoma,lung adenocarcinoma,lung squamous cell carcinoma,prostate carcinoma.Using R language to analyze TCGATARGETGTEx dataset,it was found that BTN3A1 was closely related to immune cell infiltration in pan-cancer.BTN3A1 expression elevated remarkably in HCC tissues compared with adjacent normal tissues,both in the m RNA and protein levels.Gene set enrichment analysis GO,KEGG,GSEA showed that BTN3A1 was remarkably related to a variety of signaling pathways that may be related to immunity.Immune infiltrate analysis between BTN3A1 and immune cells showed that BTN3A1 was associated with the immune infiltration of B cell,CD8+T cell,CD4+T cell 、Macrophage,Neutrophil,and Dendritic cell(P<0.05).Conclusion:(1)BTN3A1 is dysregulated in pan-cancer,and is closely related to immune cell infiltration in pan-cancer,suggesting that BTN3A1 may play an important role in the tumor immune microenvironment.(2)BTN3A1 was highly expressed in hepatocellular carcinoma tissues.(3)BTN3A1 is closely related to a variety of immune-related signaling pathways,and is significantly correlated with a variety of immune cell infiltration in HCC.Its gene expression may regulate the progression of HCC by influencing tumor immune microenvironment.