Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Clinical Trial Center, Harbin Medical University Cancer Hospital, Harbin, China.
Front Immunol. 2022 Feb 22;13:806877. doi: 10.3389/fimmu.2022.806877. eCollection 2022.
The presence of infiltrating CD8 T lymphocytes in the tumor microenvironment of lung adenocarcinoma (LUAD) is correlated with improved patient prognosis, but underlying regulatory mechanisms remain unknown. To identify biomarkers to improve early diagnosis and treatment of LUAD, we downloaded 13 immune cell line-associated datasets from the GEO database. We identified CD8 T cell-associated genes weighted correlation network analysis. We constructed molecular subtypes based on CD8 T cell-associated genes and constructed a multi-gene signature. We identified 252 CD8 T cell-associated genes significantly enriched in immune function-related pathways and two molecular subtypes of LUAD (immune cluster 1 [IC1] and IC2) using our CD8 T cell-associated gene signature. Patients with the IC2 subtype had a higher tumor mutation burden and lower immune infiltration scores, whereas those with the IC1 subtype were more sensitive to immune checkpoint inhibitors. Prioritizing the top candidate genes to construct a 10-gene signature, we validated our model using independent GSE and TCGA datasets to confirm its robustness and stable prognostic ability. Our risk model demonstrated good predictive efficacy using the Imvigor210 immunotherapy dataset. Thus, we established a novel and robust CD8 T cell-associated gene signature, which could help assess prognostic risk and immunotherapy response in LUAD patients.
肺腺癌 (LUAD) 肿瘤微环境中浸润性 CD8 T 淋巴细胞的存在与改善患者预后相关,但潜在的调节机制尚不清楚。为了确定改善 LUAD 早期诊断和治疗的生物标志物,我们从 GEO 数据库中下载了 13 个免疫细胞系相关数据集。我们使用加权相关网络分析识别与 CD8 T 细胞相关的基因。我们基于 CD8 T 细胞相关基因构建了分子亚型,并构建了多基因特征。我们使用 CD8 T 细胞相关基因特征鉴定了 252 个在免疫功能相关途径中显著富集的 CD8 T 细胞相关基因,并鉴定了 LUAD 的两种分子亚型(免疫簇 1 [IC1]和 IC2)。IC2 亚型患者的肿瘤突变负担较高,免疫浸润评分较低,而 IC1 亚型患者对免疫检查点抑制剂更敏感。通过优先考虑顶级候选基因来构建 10 基因特征,我们使用独立的 GSE 和 TCGA 数据集验证了我们的模型,以确认其稳健性和稳定的预后能力。我们的风险模型使用 Imvigor210 免疫治疗数据集证明了良好的预测效果。因此,我们建立了一个新的稳健的 CD8 T 细胞相关基因特征,可帮助评估 LUAD 患者的预后风险和免疫治疗反应。