癌症进展过程中肿瘤特异性抗原的表达可以触发针对肿瘤的免疫反应。在这里，我们研究由非规范开放阅读框（ncORF）编码的微生物蛋白是否是肿瘤特异性抗原的相关来源。我们分析了 117 个肝细胞癌 (HCC) 肿瘤和匹配的健康组织的 RNA 测序数据以及核糖体分析和免疫肽组学数据。结合人类白细胞抗原表位结合预测和实验验证实验，我们得出结论，HCC中大约40%的肿瘤特异性抗原很可能源自ncORF，其中包括两种可以在人源化小鼠中触发免疫反应的肽。我们鉴定了 33 个肿瘤特异性长非编码 RNA 的子集，这些子集表达新的癌症抗原，这些抗原在所分析的 HCC 样本中超过 10% 共有，合并后覆盖了很大一部分患者。该研究的结果为扩大抗癌疫苗的范围开辟了途径。

The expression of tumor-specific antigens during cancer progression can trigger an immune response against the tumor. Here, we investigate if microproteins encoded by noncanonical open reading frames (ncORFs) are a relevant source of tumor-specific antigens. We analyze RNA sequencing data from 117 hepatocellular carcinoma (HCC) tumors and matched healthy tissue together with ribosome profiling and immunopeptidomics data. Combining human leukocyte antigen-epitope binding predictions and experimental validation experiments, we conclude that around 40% of the tumor-specific antigens in HCC are likely to be derived from ncORFs, including two peptides that can trigger an immune response in humanized mice. We identify a subset of 33 tumor-specific long noncoding RNAs expressing novel cancer antigens shared by more than 10% of the HCC samples analyzed, which, when combined, cover a large proportion of the patients. The results of the study open avenues for extending the range of anticancer vaccines.