Institute of Radiation Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Technical University Munich (TUM), Germany.
Mol Oncol. 2020 May;14(5):917-932. doi: 10.1002/1878-0261.12670. Epub 2020 Apr 1.
Mast cells are a major component of the immune microenvironment in tumour tissues and modulate tumour progression by releasing pro-tumorigenic and antitumorigenic molecules. Regarding the impact of mast cells on the outcomes of patients with lung adenocarcinoma (LUAD) patient, several published studies have shown contradictory results. Here, we aimed at elucidating the role of mast cells in early-stage LUAD. We found that high mast cell abundance was correlated with prolonged survival in early-stage LUAD patients. The mast cell-related gene signature and gene mutation data sets were used to stratify early-stage LUAD patients into two molecular subtypes (subtype 1 and subtype 2). The neural network-based framework constructed with the mast cell-related signature showed high accuracy in predicting response to immunotherapy. Importantly, the prognostic mast cell-related signature predicted the survival probability and the potential relationship between TP53 mutation, c-MYC activation and mast cell activities. The meta-analysis confirmed the prognostic value of the mast cell-related gene signature. In summary, this study might improve our understanding of the role of mast cells in early-stage LUAD and aid in the development of immunotherapy and personalized treatments for early-stage LUAD patients.
肥大细胞是肿瘤组织中免疫微环境的主要组成部分,通过释放促肿瘤和抗肿瘤分子来调节肿瘤的进展。关于肥大细胞对肺腺癌 (LUAD) 患者结局的影响,已有几项已发表的研究结果相互矛盾。在这里,我们旨在阐明肥大细胞在早期 LUAD 中的作用。我们发现,早期 LUAD 患者中肥大细胞丰度高与生存时间延长相关。利用肥大细胞相关基因特征和基因突变数据集将早期 LUAD 患者分为两个分子亚型(亚型 1 和亚型 2)。基于肥大细胞相关特征构建的神经网络框架在预测免疫治疗反应方面具有很高的准确性。重要的是,预测预后的肥大细胞相关基因特征预测了生存概率以及 TP53 突变、c-MYC 激活和肥大细胞活性之间的潜在关系。荟萃分析证实了肥大细胞相关基因特征的预后价值。总之,本研究可能有助于提高我们对肥大细胞在早期 LUAD 中的作用的认识,并有助于为早期 LUAD 患者制定免疫治疗和个性化治疗方案。