A new immune signature for survival prediction and immune checkpoint molecules in lung adenocarcinoma
A new immune signature for survival prediction and immune checkpoint molecules in lung adenocarcinoma
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DOI：
10.1186/s12967-020-02286-z
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发表时间：
2020-03-06
影响因子：
7.4
通讯作者：
Zhu, Jiaona
中科院分区：
文献类型：
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作者：
Guo, Dina;Wang, Mian;Zhu, Jiaona
背景肺腺癌是肺癌中最常见的亚型。预后标志可以可靠地根据风险对LUAD患者进行分层，这有助于系统治疗的管理。在这项研究中，系统和可靠的免疫信号被用来评估LUAD的预后分层。方法将LUAD患者的免疫相关基因图谱作为一个TCGA训练集：494个，其他验证集1：226个，验证集2：n=398个。用单变量Cox生存分析从每个队列中确定候选免疫相关基因。然后，开发了免疫签名，并在训练和验证集中进行了验证。结果在本研究中，功能分析表明免疫相关基因参与了免疫调节和MAPK信号通路。训练集中建立了基于10个免疫相关基因的预后标志，并将患者分为高风险组和低风险组。我们的10个免疫相关基因特征与较差的存活率显著相关，尤其是在肿瘤早期。进一步的分层分析显示，这10个免疫相关基因信号仍然是预测吸烟或不吸烟患者、KRAS突变患者或KRAS野生型患者、EGFR突变患者或EGFR野生型患者预后的有效工具。我们的信号与B细胞、CD4+T细胞、CD8+T细胞、中性粒细胞、树突状细胞(DC)和巨噬细胞免疫浸润以及免疫检查点分子PD-1和CTLA-4呈负相关(P<；0.05)。结论本研究结果表明，我们的签名是一种有希望的生物标志物，可以预测LUAD的预后，并有助于LUAD免疫治疗的管理。
Background Lung adenocarcinoma (LUAD) is the most frequent subtype of lung cancer. The prognostic signature could be reliable to stratify LUAD patients according to risk, which helps the management of the systematic treatments. In this study, a systematic and reliable immune signature was performed to estimate the prognostic stratification in LUAD. Methods The profiles of immune-related genes for patients with LUAD were used as one TCGA training set: n = 494, other validation set 1: n = 226 and validation set 2: n = 398. Univariate Cox survival analysis was used to identify the candidate immune-related genes from each cohort. Then, the immune signature was developed and validated in the training and validation sets. Results In this study, functional analysis showed that immune-related genes involved in immune regulation and MAPK signaling pathway. A prognostic signature based on 10 immune-related genes was established in the training set and patients were divided into high-risk and low-risk groups. Our 10 immune-related gene signature was significantly related to worse survival, especially during early-stage tumors. Further stratification analyses revealed that this 10 immune-related gene signature was still an effective tool for predicting prognosis in smoking or nonsmoking patients, patients with KRAS mutation or KRAS wild-type, and patients with EGFR mutation or EGFR wild-type. Our signature was negatively correlated with B cell, CD4+ T cell, CD8+ T cell, neutrophil, dendritic cell (DC), and macrophage immune infiltration, and immune checkpoint molecules PD-1 and CTLA-4 (P < 0.05). Conclusions These findings suggested that our signature was a promising biomarker for prognosis prediction and can facilitate the management of immunotherapy in LUAD.