Neoantigens Derived from Recurrently Mutated Genes as Potential Immunotherapy Targets for Gastric Cancer
Neoantigens Derived from Recurrently Mutated Genes as Potential Immunotherapy Targets for Gastric Cancer
复制标题
反复突变基因衍生的新抗原作为胃癌潜在免疫治疗靶点
DOI：
10.1155/2019/8103142
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发表时间：
2019-01-01
影响因子：
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通讯作者：
Chen, Shuqing
中科院分区：
文献类型：
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作者：
Zhou, Jie;Zhao, Wenyi;Chen, Shuqing
新抗原是基于T细胞的免疫疗法的最佳肿瘤特异性靶标，特别是对于具有不可治疗的突变驱动基因的患者。T细胞免疫治疗可以成为HLA基因型患者共享相同致癌突变的通用治疗方法。为了鉴定用于治疗胃癌的潜在新抗原，32名胃癌患者参加了我们的研究。通过TSNAD软件处理来自这些患者的全外显子组测序数据以检测癌症体细胞突变并预测新抗原。不同患者之间的体细胞突变表明患者间存在高度异质性。C>A和C>T取代是常见的，表明活性核苷酸切除修复。与T2或T4b期患者相比，T1a期患者的预测新抗原数量显著更高。在我们的研究中发现了6个基因（PIK3CA、FAT4、BRCA2、GNAQ、LRP 1B和PREX 2）作为反复突变的驱动基因。结合高频率的HLA等位基因，来自六个复发突变基因的几种新抗原被认为是进一步免疫治疗的潜在靶点。
Neoantigens are optimal tumor-specific targets for T-cell based immunotherapy, especially for patients with undruggable mutated driver genes. T-cell immunotherapy can be a universal treatment for HLA genotype patients sharing same oncogenic mutations. To identify potential neoantigens for therapy in gastric cancer, 32 gastric cancer patients were enrolled in our study. Whole exome sequencing data from these patients was processed by TSNAD software to detect cancer somatic mutations and predict neoantigens. The somatic mutations between different patients suggested a high interpatient heterogeneity. C>A and C>T substitutions are common, suggesting an active nucleotide excision repair. The number of predicted neoantigens was significantly higher in patients at stage T1a compared to in patients at T2 or T4b. Six genes (PIK3CA, FAT4, BRCA2, GNAQ, LRP1B, and PREX2) were found as recurrently mutated driver genes in our study. Combining with highly frequent HLA alleles, several neoantigens derived from six recurrently mutated genes were considered as potential targets for further immunotherapy.