PDF(Pubmed)
Abstract：
UNASSIGNED: It is still unclear whether KEAP1 mutation is detrimental to immunotherapy of lung adenocarcinoma (LUAD) patients, we try to analyse the exact changes in the TME in LUAD patients with KEAP1 mutations and to identify key factors influencing prognosis.
UNASSIGNED: A total of 1,029 patients with lung squamous carcinoma (LUSC) or LUAD with data obtained from The Cancer Genome Atlas were included in this study. The TME and OS of patients with LUAD stratified by mutant versus wild-type KEAP1 status were comprehensively measured. Moreover, we classified LUAD patients with KEAP1 mutations into three subtypes, by unsupervised consensus clustering. We further analysed the TME, OS, commutated genes and metabolic pathways of different subgroups. A total of 40 LUAD patients underwent immunotherapy were collected and classified into mutant KEAP1 group and wild-type KEAP1 group. We also conducted immunohistochemical staining in KEAP1-MT groups.
UNASSIGNED: Suppressed TME was observed not only in LUAD patients but also in LUSC patients. LUAD patients with mutant KEAP1 underwent immunotherapy had worse PFS than wild-type KEAP1. Unsupervised consensus clustering analysis suggested that the three subtypes of patients exhibited different densities of neutrophil infiltration and had different OS results: cluster 2 patients had significantly higher levels of neutrophils had significantly worse prognoses than those of patients in clusters 1 and 3 and patients with wild-type KEAP1. Univariate and multivariate Cox analyses proved that a high density of neutrophils was significantly associated with worse OS and immunohistochemical staining proved that shorter PFS showed high density of neutrophils.
UNASSIGNED: KEAP1 mutation significantly suppresses the tumour immune microenvironment in LUAD patients. LUAD patients with mutant KEAP1 underwent immunotherapy had worse PFS than with wild-type KEAP1. Neutrophils may play an important role in the prognosis of LUAD patients with KEAP1 mutations and may provide a promising therapeutic target.
UNASSIGNED: A total of 1,029 patients with lung squamous carcinoma (LUSC) or LUAD with data obtained from The Cancer Genome Atlas were included in this study. The TME and OS of patients with LUAD stratified by mutant versus wild-type KEAP1 status were comprehensively measured. Moreover, we classified LUAD patients with KEAP1 mutations into three subtypes, by unsupervised consensus clustering. We further analysed the TME, OS, commutated genes and metabolic pathways of different subgroups. A total of 40 LUAD patients underwent immunotherapy were collected and classified into mutant KEAP1 group and wild-type KEAP1 group. We also conducted immunohistochemical staining in KEAP1-MT groups.
UNASSIGNED: Suppressed TME was observed not only in LUAD patients but also in LUSC patients. LUAD patients with mutant KEAP1 underwent immunotherapy had worse PFS than wild-type KEAP1. Unsupervised consensus clustering analysis suggested that the three subtypes of patients exhibited different densities of neutrophil infiltration and had different OS results: cluster 2 patients had significantly higher levels of neutrophils had significantly worse prognoses than those of patients in clusters 1 and 3 and patients with wild-type KEAP1. Univariate and multivariate Cox analyses proved that a high density of neutrophils was significantly associated with worse OS and immunohistochemical staining proved that shorter PFS showed high density of neutrophils.
UNASSIGNED: KEAP1 mutation significantly suppresses the tumour immune microenvironment in LUAD patients. LUAD patients with mutant KEAP1 underwent immunotherapy had worse PFS than with wild-type KEAP1. Neutrophils may play an important role in the prognosis of LUAD patients with KEAP1 mutations and may provide a promising therapeutic target.
摘要：
■目前尚不清楚KEAP1突变是否对肺腺癌（LUAD）患者的免疫治疗有害，我们试图分析KEAP1突变的LUAD患者TME的确切变化,并确定影响预后的关键因素.
■本研究共纳入1,029例肺鳞癌（LUSC）或LUAD患者，数据来自癌症基因组图谱。通过突变型与野生型KEAP1状态分层的LUAD患者的TME和OS进行综合测量。此外，我们将LUAD患者KEAP1突变分为三种亚型，通过无监督的共识聚类。我们进一步分析了TME，操作系统,不同亚组的交换基因和代谢途径。收集40例接受免疫治疗的LUAD患者，分为突变型KEAP1组和野生型KEAP1组。我们还在KEAP1-MT组中进行了免疫组织化学染色。
■不仅在LUAD患者而且在LUSC患者中观察到TME抑制。患有突变KEAP1的LUAD患者接受免疫治疗的PFS比野生型KEAP1更差。无监督共识聚类分析表明，三种亚型的患者表现出不同的中性粒细胞浸润密度，并且具有不同的OS结果：第2组患者的中性粒细胞水平明显高于第1组和第3组患者以及野生型KEAP1患者的预后明显较差。单变量和多变量Cox分析证明，嗜中性粒细胞的高密度与OS恶化显着相关，免疫组织化学染色证明，较短的PFS显示嗜中性粒细胞的高密度。
■KEAP1突变显著抑制LUAD患者的肿瘤免疫微环境。患有突变KEAP1的LUAD患者接受免疫治疗的PFS比野生型KEAP1更差。中性粒细胞可能在KEAP1突变的LUAD患者的预后中起重要作用，并可能提供有希望的治疗靶标。
■本研究共纳入1,029例肺鳞癌（LUSC）或LUAD患者，数据来自癌症基因组图谱。通过突变型与野生型KEAP1状态分层的LUAD患者的TME和OS进行综合测量。此外，我们将LUAD患者KEAP1突变分为三种亚型，通过无监督的共识聚类。我们进一步分析了TME，操作系统,不同亚组的交换基因和代谢途径。收集40例接受免疫治疗的LUAD患者，分为突变型KEAP1组和野生型KEAP1组。我们还在KEAP1-MT组中进行了免疫组织化学染色。
■不仅在LUAD患者而且在LUSC患者中观察到TME抑制。患有突变KEAP1的LUAD患者接受免疫治疗的PFS比野生型KEAP1更差。无监督共识聚类分析表明，三种亚型的患者表现出不同的中性粒细胞浸润密度，并且具有不同的OS结果：第2组患者的中性粒细胞水平明显高于第1组和第3组患者以及野生型KEAP1患者的预后明显较差。单变量和多变量Cox分析证明，嗜中性粒细胞的高密度与OS恶化显着相关，免疫组织化学染色证明，较短的PFS显示嗜中性粒细胞的高密度。
■KEAP1突变显著抑制LUAD患者的肿瘤免疫微环境。患有突变KEAP1的LUAD患者接受免疫治疗的PFS比野生型KEAP1更差。中性粒细胞可能在KEAP1突变的LUAD患者的预后中起重要作用，并可能提供有希望的治疗靶标。
