Analysis of Lung Adenocarcinoma Subtypes Based on Immune Signatures Identifies Clinical Implications for Cancer Therapy
Analysis of Lung Adenocarcinoma Subtypes Based on Immune Signatures Identifies Clinical Implications for Cancer Therapy
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基于免疫特征的肺腺癌亚型分析确定了癌症治疗的临床意义
DOI：
10.1016/j.omto.2020.03.021
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发表时间：
2020-06-26
影响因子：
5.7
通讯作者：
Chen, Yong-song
中科院分区：
文献类型：
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作者：
Xu, Feng;Chen, Jie-xin;Chen, Yong-song
肺癌是世界范围内最常见的癌症死亡原因，而肺腺癌（LUAD）是最常见的组织学亚型。然而，由于这种癌症类型的异质性，预后和预测结果有所不同。LUAD亚型是根据29个免疫特征的免疫基因组图谱确定的。我们命名了三种LUAD亚型：免疫力高、免疫力中等和免疫力低。免疫高亚型的特征是免疫激活，如免疫评分升高，基质评分升高，CD8(+) T细胞浸润最高，肿瘤纯度降低。在免疫高亚型中也观察到人白细胞抗原（HLA）基因、免疫检查点分子和T辅助1 (Th1)/干扰素γ (IFN γ)基因标记的激活表达。与癌症起始和进展相关的n -6-甲基腺苷（m(6)A） RNA甲基化在免疫高亚型中降低。功能和信号通路富集分析进一步表明，免疫高亚型与其他亚型之间的差异表达基因主要参与免疫应答和一些癌症相关通路。此外，免疫高亚型对免疫治疗和化疗更敏感。最后，确定了针对LUAD亚型分化的候选化合物。基于免疫特征全面表征LUAD亚型可能有助于提供LUAD治疗的潜在策略。
Lung cancer is the most common cause of cancer deaths worldwide, and lung adenocarcinoma (LUAD) is the most common histological subtype. However, the prognostic and predictive outcomes differ because of this cancer type heterogeneity. LUAD subtypes were identified on the basis of the immunogenomic profiling of 29 immune signatures. We named three LUAD subtypes: Immunity High, Immunity Medium, and Immunity Low. The Immunity High subtype was characterized by immune activation, e.g., increased immune scores, elevated stromal scores and the highest infiltration of CD8(+) T cells, and decreased tumor purities. Activated expressions of human leukocyte antigen (HLA) genes, immune checkpoint molecules, and T helper 1 (Th1)/interferon-gamma (IFN gamma) gene signature were also observed in the Immunity High subtype. N-6-methyladenosine (m(6)A) RNA methylation, associated with cancer initiation and progression, was reduced in the Immunity High subtype. Functional and signaling pathway enrichment analysis further showed that differentially expressed genes between the Immunity High subtype and the other subtypes mainly participated in immune response and some cancerassociated pathways. In addition, the Immunity High subtype exhibited more sensitivity to immunotherapy and chemotherapy. Finally, candidate compounds that aimed at LUAD subtype differentiation were identified. Comprehensively characterizing the LUAD subtypes based on immune signatures may help to provide potential strategies for LUAD treatment.