One gene could be transcribed to different RNA isoforms, and then produce various forms of protein sequences. This mechanism largely diversifies the cellular pool and allows natural selection to select from a wider range of substrates. In the cancer field, the isoform switches between tumor and normal tissues, such as the alternative splicing, stop codon read-through, or protein domestication, are significantly ignored by the traditional differential expression analyses. The intention of this work is to fill this gap. We collected public transcriptome and translatome data from ten patients with liver cancer, and performed genome-wide comparison on the stop codon read-through and protein domestication events. Both events diversify the proteome during long-term evolution. Surprisingly, we found that the tumor tissues globally have higher occurrence of stop codon read-through events as well as protein domestication events (translation signals of non-coding repetitive elements). These read-through and domestication events show limited overlapping across the ten patients, indicating the randomness of their occurrence and their deleterious nature. These tumor-specific events might have been purged by natural selection if they are not collected timely. Our work manifests the role of protein extension and domestication in liver cancer oncogenesis, adding new aspects to the cancer field.

一个基因可以转录成不同的RNA异构体，然后产生各种形式的蛋白质序列。这种机制在很大程度上使细胞池多样化，并允许自然选择从更广泛的基质中进行选择。在癌症领域，传统的差异表达分析明显忽略了肿瘤和正常组织之间的异构体转换，例如选择性剪接、终止密码子通读或蛋白质驯化。这项工作的目的是填补这一空白。我们收集了 10 名肝癌患者的公开转录组和翻译组数据，并对终止密码子通读和蛋白质驯化事件进行了全基因组比较。这两个事件在长期进化过程中使蛋白质组多样化。出奇，我们发现全球肿瘤组织中终止密码子通读事件以及蛋白质驯化事件（非编码重复元件的翻译信号）的发生率更高。这些通读和驯化事件在十名患者中显示出有限的重叠，表明它们发生的随机性及其有害性质。如果没有及时收集这些肿瘤特异性事件，它们可能已被自然选择清除。我们的工作证明了蛋白质延伸和驯化在肝癌肿瘤发生中的作用，为癌症领域增加了新的方面。表明它们发生的随机性及其有害性质。如果没有及时收集这些肿瘤特异性事件，它们可能已被自然选择清除。我们的工作证明了蛋白质延伸和驯化在肝癌肿瘤发生中的作用，为癌症领域增加了新的方面。表明它们发生的随机性及其有害性质。如果没有及时收集这些肿瘤特异性事件，它们可能已被自然选择清除。我们的工作证明了蛋白质延伸和驯化在肝癌肿瘤发生中的作用，为癌症领域增加了新的方面。