DNA methylation-based lung adenocarcinoma subtypes can predict prognosis, recurrence, and immunotherapeutic implications.
DNA methylation-based lung adenocarcinoma subtypes can predict prognosis, recurrence, and immunotherapeutic implications.
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基于 DNA 甲基化的肺腺癌亚型可以预测预后、复发和免疫治疗影响
DOI：
10.18632/aging.104129
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发表时间：
2020-11-21
期刊：
影响因子：
--
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Xu F;He L;Zhan X;Chen J;Xu H;Huang X;Li Y;Zheng X;Lin L;Chen Y
肺腺癌（LUAD）的高度异质性使其诊断和治疗困难。此外，异常的DNA甲基化谱有助于肿瘤异质性并改变免疫应答。我们使用来自公开数据库的DNA甲基化阵列数据来建立LUAD预后的预测模型。33个甲基化位点被确定为特异性预后生物标志物，与患者的临床特征无关。这些甲基化谱用于鉴定潜在的候选药物，并研究LUAD的免疫微环境和对免疫治疗的反应。与高危组相比，低危组复发率低，预后好。两组之间的肿瘤微环境不同，反映在低风险组中静息树突状细胞数量较多，单核细胞和静息肥大细胞数量较少。此外，低风险患者报告了较高的免疫和间质评分，较低的肿瘤纯度和较高的HLA基因表达。低风险患者对免疫治疗反应良好，因为免疫检查点分子表达较高，干性指数较低。因此，我们的模型预测了低风险甲基化组患者的良好预后和总生存期增加。此外，该模型可以提供潜在的药物靶点，以开发针对LUAD的有效免疫疗法。
The marked heterogeneity of lung adenocarcinoma (LUAD) makes its diagnosis and treatment difficult. In addition, the aberrant DNA methylation profile contributes to tumor heterogeneity and alters the immune response. We used DNA methylation array data from publicly available databases to establish a predictive model for LUAD prognosis. Thirty-three methylation sites were identified as specific prognostic biomarkers, independent of patients’ clinical characteristics. These methylation profiles were used to identify potential drug candidates and study the immune microenvironment of LUAD and response to immunotherapy. When compared with the high-risk group, the low-risk group had a lower recurrence rate and favorable prognosis. The tumor microenvironment differed between the two groups as reflected by the higher number of resting dendritic cells and a lower number of monocytes and resting mast cells in the low-risk group. Moreover, low-risk patients reported higher immune and stromal scores, lower tumor purity, and higher expression of HLA genes. Low-risk patients responded well to immunotherapy due to higher expression of immune checkpoint molecules and lower stemness index. Thus, our model predicted a favorable prognosis and increased overall survival for patients in the low-risk methylation group. Further, this model could provide potential drug targets to develop effective immunotherapies for LUAD.
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影响因子：
4.6
作者：
Ferraresso S;Aricò A;Sanavia T;Da Ros S;Milan M;Cascione L;Comazzi S;Martini V;Giantin M;Di Camillo B;Mazzariol S;Giannuzzi D;Marconato L;Aresu L
通讯作者：
Aresu L
影响因子：
64.5
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Malta TM;Sokolov A;Gentles AJ;Burzykowski T;Poisson L;Weinstein JN;Kamińska B;Huelsken J;Omberg L;Gevaert O;Colaprico A;Czerwińska P;Mazurek S;Mishra L;Heyn H;Krasnitz A;Godwin AK;Lazar AJ;Cancer Genome Atlas Research Network;Stuart JM;Hoadley KA;Laird PW;Noushmehr H;Wiznerowicz M
通讯作者：
Wiznerowicz M
影响因子：
4.4
作者：
Bae, Jooeun;Mitsiades, Constantine;Munshi, Nikhil C.
通讯作者：
Munshi, Nikhil C.
影响因子：
4.4
作者：
Pacheco, Rodrigo;Oliva, Harold;Franco, Rafael
通讯作者：
Franco, Rafael
影响因子：
7.5
作者：
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通讯作者：
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