ADAR1 is a prognostic biomarker and is correlated with immune infiltration in lung adenocarcinoma.
ADAR1 is a prognostic biomarker and is correlated with immune infiltration in lung adenocarcinoma.
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肺腺癌(LUAD)是非小细胞肺癌中常见的一种亚型，其发病率和死亡率较高，且因其早期发生转移而被发现于晚期。腺苷脱氨酶RNA特异性1(ADAR1)是一种催化腺苷到肌苷编辑的重要生理过程的RNA编辑酶，已被证明参与了LUAD的进展。越来越多的证据表明，肿瘤免疫微环境的免疫渗透对大多数人类实体器官恶性肿瘤具有预后价值；然而，ADAR1的功能尚不清楚。在癌症基因组图谱-LUAD数据库中分析ADAR1的表达，并在我们的LUAD队列中进行验证。为了评估ADAR1的预后价值，在LUAD队列中进行了Kaplan-Meier生存分析和Cox回归分析。ADAR1和LUAD之间的联系通过细胞类型鉴定的分析，通过估计已知RNA转录本的相对亚集来渗透。此外，采用多重免疫组织化学方法证实ADAR1在LUAD患者中的表达与免疫细胞的关系。ADAR1在LUAD组织中高表达，且与淋巴结转移(p <； 0.0 1)、肿瘤分期(p <； 0.0 5)及患者预后不良(p <； 0.0 1)密切相关。ADAR1高表达的LUAD可转移到比原发灶表达更多ADAR1的淋巴结。此外，在ADAR1高表达的LUAD组织中，M0巨噬细胞和M2巨噬细胞增多，而CD4+T细胞减少。淋巴结转移灶中ADAR1的表达与CD_4~+T细胞(p = 0.0017)和M_1巨噬细胞(p = 0.0037)含量呈负相关。我们的研究结果提示ADAR1可能有助于LUAD患者的预后和LNM的预测，并有望成为LUAD患者免疫相关的分子靶点。
Lung adenocarcinoma (LUAD) is a common subtype of non‐small cell lung cancer with high morbidity and mortality rates and is usually detected at advanced stages because of the early onset of metastasis. Adenosine deaminase RNA‐specific 1 (ADAR1) is an RNA editing enzyme that catalyzes the important physiological process of adenosine‐to‐inosine editing and has been shown to participate in the progression of LUAD. Increasing evidence has suggested that immune infiltration of the tumor immune microenvironment has prognostic value for most human solid organ malignancies; however, much is unknown about the functions of ADAR1. The expression of ADAR1 was analyzed in The Cancer Genome Atlas ‐LUAD database and validated in our LUAD cohort. To assess the prognostic value of ADAR1, Kaplan‐Meier survival analyses and Cox regression analyses were carried out in LUAD cohorts. The association between ADAR1 and LUAD immune infiltrates via analyses of cell‐type identification by estimating relative subsets of known RNA transcripts. Furthermore, multiplex immunohistochemistry was used to confirm the relationship between ADAR1 expression and immune cells in the present cohort of patients with LUAD. ADAR1 was highly expressed in LUAD tissues and closely correlated with lymph node metastasis (LNM) (p < 0.01), advanced tumor stage (p < 0.05), and poor patient prognosis (p < 0.01), thus indicating that increased ADAR1 contributed to the progression of LUAD. LUAD with high ADAR1 expression can metastasize to lymph nodes that express more ADAR1 than the primary lesion. In addition, M0 macrophages and M2 macrophages increased and CD4+T cells decreased in LUAD tissues with high ADAR1 expression. And the expression of ADAR1 in lymph node metastases was negatively correlated with the contents of CD4+T cells (p = 0.0017) and M1 macrophages (p = 0.0037). The findings of our study suggested that ADAR1 may be useful in predicting prognosis and LNM in LUAD, and may serve as a promising immune‐related molecular target for LUAD patients.
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肿瘤免疫治疗中骨髓源性抑制细胞的概况
影响因子：
11.1
作者：
Hao Z;Li R;Wang Y;Li S;Hong Z;Han Z
通讯作者：
Han Z
影响因子：
16.6
作者：
Alonso R;Flament H;Lemoine S;Sedlik C;Bottasso E;Péguillet I;Prémel V;Denizeau J;Salou M;Darbois A;Núñez NG;Salomon B;Gross D;Piaggio E;Lantz O
通讯作者：
Lantz O
影响因子：
50.3
作者：
Hanahan, Douglas;Coussens, Lisa M.
通讯作者：
Coussens, Lisa M.
影响因子：
64.8
作者：
Ishizuka, Jeffrey J.;Manguso, Robert T.;Haining, W. Nicholas
通讯作者：
Haining, W. Nicholas
DOI：
10.1038/nri3073
发表时间：
2011-10-14
期刊：
Nature reviews. Immunology
影响因子：
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作者：
通讯作者：
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