Bioinformatics Analysis On HLA-A2 Restricted Mutated Neoantigen Epitopes Of Breast Cancer

Objective and significanceBreast cancer is the most common malignant tumor in women.Currently,comprehensive treatment methods including surgery,chemotherapy,radiotherapy,endocrine therapy and targeted therapy are used clinically,and most patients with early and a few patients with mid-stage breast cancer have achieved a good prognosis.However,there is still a lack of very effective treatment for advanced and some mid-stage breast cancer patients,and currently used chemotherapy and other treatment methods are highly toxic and costly,which not only reduce the quality of life of breast cancer patients,but also increase the burden on the family and society.Therefore,breast cancer is a serious public health problem.There is a need to develop new therapies to help improve outcomes in these patients.Neoantigen peptide vaccine is a kind of therapeutic vaccine which can induce the formation of specific anti-tumor T cells by using epitope peptide formed by tumor mutation as antigen.It can be divided into individual neoantigen vaccines and "universal" neoantigen vaccines."Universal" new vaccine antigens.is refers to the use of the crowd as the target of the vaccine of the communist party of China have mutations,is different from the individual neo-antigen vaccine,it doesn't require surgery for tissue samples to high-throughput sequencing.It takes less time and costs less and it can specifically kill tumor cells."Universal" neoantigen vaccines have great potential for development.In this study,HLA-A2 restriction neoantigen candidate epitopes were screened by bioinformatics method,which provided an important basis for the preparation of universal neoantigen vaccine for breast cancer.Research methodsWe obtained sequence from the published literature and data In SNPS,TCGA,SNP4disease public database,and used effective HLA-A2 antigen epitope prediction tool BIMAS,SYFPEITHI and NetMHC4.0 that based on artificial neural network prediction of breast cancer to predict the neoantigen peptides.NetMHC prediction score less than or equal to 2 tables can be a candidate of peptides.The higherBIMAS and SYFPEITHI prediction scores,the stronger binding force between the neoantigen peptides and MHC molecules.The TAP-pre tool was used to predict the binding force of the neoantigen peptides screened by the above 3 software,and the epitopes whose binding force was lower than Intermediate were eliminated.The candidate epitopes were ranked in priority according to mutation frequency and predicted score.ResultsA total of 17 mutant genes,including NBPF12,XPO1,Clec18,ErBB2,CDC42BPA,PCDHGB4,PTPRZ1,golga6L6,GSTP1,BRCA2,NCOA1,ATM,PALB2,BTLA,ATR,LHCGRSTON1-GTF2A1L and EGFR,were selected using the above methods.There were 26 relatively high frequency neoantigen epitopes,and the predicted binding ability scores of 26 neoantigen epitopes were significantly different(P<0.05).The predicted score of included neoantigen NetMHC was less than or equal to 2.Among them,the epitopes with relatively high mutation frequency are GSTP1(A114V)(mutation frequency 5.94%),BRCA2(N991H)(mutation frequency 5.40%),NCOA1(P1272S)(mutation frequency 1.69%),ATM(D126E)(mutation frequency 1.57%),NBPF12(E125Q)(mutation frequency 1.48%),ATM(L1420F)(mutation frequency 1.12%).ConclusionThrough screening HLA-A2 neoantigen epitope polypeptide in breast cancer,it was found that the common mutation of breast cancer was lower than that of other tumors.It is difficult to find "universal" neoantigen epitopes of breast cancer.Universal neoantigen vaccines may not be suitable for breast cancer,and"individualized" neoantigen vaccines may be more promising,but further studies are needed to confirm this viewpoint.