Dysregulation in nucleic acid-sensing pathway genes is associated with cancer patients' prognosis
Dysregulation in nucleic acid-sensing pathway genes is associated with cancer patients' prognosis
复制标题
核酸传感通路基因的失调与癌症患者的预后相关
DOI：
10.1111/cas.14450
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发表时间：
2020-06-11
期刊：
影响因子：
5.7
通讯作者：
Tian, Xin-Xia
中科院分区：
文献类型：
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作者：
Huo, Yan-Fei;Han, Yang;Tian, Xin-Xia
先天免疫系统是抵抗病原体的第一道防线，它被来自微生物入侵者的核酸激活，这些核酸被核酸感应受体识别。最近的证据证实了这些受体对受损癌细胞释放的核酸做出反应的能力。先天免疫系统也参与癌症免疫监视，并且可以通过靶向核酸传感途径来调节以设计有效的抗肿瘤疗法。需要对癌症中核酸传感途径的失调进行系统、全面的分析，以充分了解其作用。基于癌症基因组图谱泛癌症队列的多维数据，我们发现细胞溶质DNA敏感基因如AIM 2和CGAS的上调在肿瘤组织中很常见。我们使用核酸传感途径中的15个基因将所有肿瘤患者分为2个亚组，发现核酸传感途径基因表达较高的亚组与癌症类型的预后较差相关。但在同源重组缺陷患者中，核酸识别激活亚组与较好的预后相关，证实了核酸识别的治疗效果。该研究有助于更好地理解核酸识别在癌症中的功能和机制，为新的治疗策略奠定基础，并扩大新药开发的范围。
The innate immune system, the first line of defense against pathogens, is activated by nucleic acids from microbial invaders that are recognized by nucleic acid-sensing receptors. Recent evidence affirms the ability of these receptors to respond to nucleic acids released by damaged cancer cells. The innate immune system is also involved in cancer immunosurveillance, and could be modulated for devising effective antitumor therapies by targeting nucleic acid-sensing pathways. A systematic, comprehensive analysis of dysregulation in nucleic acid-sensing pathways in cancer is required to fully understand its role. Based on multidimensional data of The Cancer Genome Atlas pan-cancer cohort, we revealed that upregulation of cytosolic DNA-sensing genes likeAIM2andCGASwas common in tumor tissues. We used 15 genes in the nucleic acid-sensing pathway to cluster all tumor patients into 2 subgroups and found that the subgroup with higher expression of nucleic acid-sensing pathway genes was associated with poorer prognosis across cancer types. However, in homologous recombination deficient patients, the nucleic acid recognition activated subgroup was associated with better prognosis, which confirms the therapeutic effect of nucleic acid recognition. This study contributes to a better understanding of the functions and mechanisms of nucleic acid recognition in cancer, lays the foundation for new therapeutic strategies, and enlarges the scope of development of new drugs.