This study aimed to investigate the clinical significance of RNA editing (RE) and RNA editing derived (RED-) neoantigens in melanoma patients treated with immunotherapy. Vardict and VEP were used to identify the somatic mutations. RE events were identified by Reditools2 and filtered by the custom pipeline. miRTar2GO was implemented to predict the RE whether located in miRNA targets within the 3' UTR region. NetMHCpan and NetCTLpan were used to identify and characterize RED-neoantigens. In total, 7116 RE events were identified, most of which were A-to-I events. Using our custom pipeline, 631 RED-neoantigens were identified that show a significantly greater peptide-MHC affinity, and facilitate epitope processing and presentation than wild-type peptides. The OS of the patients with high RED-neoantigens burden was significantly longer (P = 0.035), and a significantly higher RED-neoantigens burden was observed in responders (P = 0.048). The area under the curve of the RED-neoantigen was 0.831 of OS. Then, we validated the reliability of RED-neoantigens in predicting the prognosis in an independent cohort and found that patients with high RED-neoantigens exhibited a longer OS (P = 0.008). To our knowledge, this is the first study to systematically assess the clinical relevance of RED-neoantigens in melanoma patients treated with immunotherapy.

中文翻译：

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来自 RNA 编辑事件的肿瘤新抗原在接受免疫治疗的黑色素瘤患者中显示出显着的临床相关性。

本研究旨在探讨 RNA 编辑 (RE) 和 RNA 编辑衍生 (RED-) 新抗原在接受免疫治疗的黑色素瘤患者中的临床意义。Vardict 和 VEP 用于鉴定体细胞突变。RE 事件由 Reditools2 识别并由自定义管道过滤。miRTar2GO 用于预测 RE 是否位于 3' UTR 区域内的 miRNA 靶标中。NetMHCpan 和 NetCTLpan 用于识别和表征 RED 新抗原。总共识别出 7116 个 RE 事件，其中大部分是 A-to-I 事件。使用我们的定制流程，鉴定出 631 种 RED-新抗原，它们比野生型肽表现出显着更高的肽-MHC 亲和力，并促进表位加工和呈递。RED-新抗原负荷高的患者的 OS 显着较长 (P = 0.035)，并且在应答者中观察到 RED-新抗原负荷显着较高 (P = 0.048)。RED-新抗原的曲线下面积为 OS 的 0.831。然后，我们在一个独立队列中验证了 RED-新抗原在预测预后方面的可靠性，发现具有高 RED-新抗原的患者表现出更长的 OS (P = 0.008)。据我们所知，这是第一项系统评估 RED-新抗原在接受免疫治疗的黑色素瘤患者中的临床相关性的研究。