摘要
目的:通过生物信息学方法筛选乳腺癌HLA-A2限制性新抗原候选表位,寻找乳腺癌新抗原高频突变位点。方法:利用NCBI、GDC数据库,从已报道的文献与测序数据中寻找乳腺癌单核苷酸变异形成的错义突变位点,通过HLA-A2抗原表位预测网站BIMAS、SYFPEITHI与基于人工神经网络的NetMHC4.0预测新抗原表位,剔除TAP结合力低于Intermediate的表位,按突变频率与预测结果对候选表位进行优先级排序。结果:使用上述方法共筛选出了BTLA、ERBB2、NBPF12等17个相对高频突变基因,共26个新抗原表位,不同表位BIMAS、SYFPEITHI预测结合力有较大差异(P<0.05),高优先级表位如GSTP1(A114V,突变频率5.94%)、BRCA2(N991H,突变频率5.40%)等有望成为新抗原候选位点,但其突变频率较低,难以做到真正的"通用",其作为乳腺癌通用新抗原疫苗表位的可能性较小。结论:乳腺癌共有突变低于其他肿瘤,寻找"通用"乳腺癌新抗原表位较为困难;"个体化"新抗原疫苗也许更有前景,但仍需要进一步研究来证实。
Objective: To screen candidate epitopes of breast cancer HLA-A2 restrictive neoantigen and to identify high frequency mutation sites in breast cancer neoantigen by using bioinformatics method. Methods: NCBI and GDC databases were used to search missense mutation sites formed by single nucleotide mutation in breast cancer among reported literatures and sequencing data. The new antigen epitopes were predicted by HLA-A2 antigen epitope prediction website BIMAS, SYFPEITHI and artificial neural networkbased NetMHC4.0, and the epitopes with TAP binding power less than Intermediate were eliminated. The candidate epitopes were prioritized by mutation frequency and prediction results. Results: A total of 17 high-frequency mutation genes, including BTLA,ERBB2 and NBPF12 etc, were screened by the above-mentioned methods, and a total of 26 neoantigen epitopes were identified. The binding power of epitopes predicted using BIMAS and SYFPEITHI showed great difference(P<0.05), epitopes in high priority as GSTP1(A114V, mutation frequency of 5.94%) and BRCA2(N991H, mutation frequency of 5.40%) etc, were expected to be candidate neo-antigen epitopes;however, their mutation frequency was relatively too low to achieve"universal use". The possibility of these epitopes used as general breast cancer neo-antigen epitopes is less likely. Conclusion: The common mutation frequency of breast cancer is lower than that of other tumors;it ’s difficult to find" universal "new antigen epitopes of breast cancer;the individualized neoantigen vaccine may be of more promise, which needs further research.
作者
游紫聪
周炜均
罗云峰
邓鉴文
张普生
冯海湛
翁俊彦
俞金龙
朱卉娟
李玉华
史福军
YOU Zicong;ZHON Weijun;LUO Yunfeng;DENG Jianwen;ZHANG Pusheng;FENG Haizhan;WENG Junyan;YU Jinlong;ZHU Huijuan;LI Yuhua;SHI Fujun(Department of Breast Surgery,Center of General Surgery,Zhujiang Hospital of Southern Medical University,Guangzhou 510282,Guangdong,China;Department of Hematology,Zhujiang Hospital of Southern Medical University,Guangzhou 510282,Guangdong,China)
出处
《中国肿瘤生物治疗杂志》
CAS
CSCD
北大核心
2020年第4期427-432,共6页
Chinese Journal of Cancer Biotherapy
基金
广东省自然科学基金资助项目(No.2014A030313334)。
关键词
乳腺癌
新抗原
HLA-A2
二代测序
breast cancer
neoantigen
HLA-A2
next-generation sequencing(NGS)
