Zhang Xun, Jiang Dizhi, Li Shunjia, Zhang Xinyu, Zheng Wendi, Cheng Bo
Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, China.
Front Oncol. 2023 Jan 12;12:1023833. doi: 10.3389/fonc.2022.1023833. eCollection 2022.
Immune-related subgroup classification in immune checkpoint blockade (ICB) therapy is largely inconclusive in lung adenocarcinoma (LUAD).
First, the single-sample Gene Set Enrichment Analysis (ssGSEA) and K-means algorithms were used to identify immune-based subtypes for the LUAD cohort based on the immunogenomic profiling of 29 immune signatures from The Cancer Genome Atlas (TCGA) database (n = 504). Second, we examined the prognostic and predictive value of immune-based subtypes using bioinformatics analysis. Survival analysis and additional COX proportional hazards regression analysis were conducted for LUAD. Then, the immune score, tumor-infiltrating immune cells (TIICs), and immune checkpoint expression of the three subtypes were analyzed. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) of the differentially expressed genes (DEGs) between three immune-based subtypes were subsequently analyzed for functional enrichment pathways.
A total of three immune-based subtypes with distinct immune signatures have been identified for LUAD and designated as cluster 1 (C1), cluster 2 (C2), and cluster 3 (C3). Patients in C3 had higher stromal, immune, and ESTIMATE scores, whereas those in C1 had the opposite. Patients in C1 had an enrichment of macrophages M0 and activation of dendritic cells, whereas tumors in C3 had an enrichment of CD8 T cells, activation of CD4 memory T cells, and macrophages M1. C3 had a higher immune cell infiltration and a better survival prognosis than other subtypes. Furthermore, patients in C3 had higher expression levels of immune checkpoint proteins such as PD-L1, PD1, CTLA4, LAG3, IDO1, and HAVCR2. No significant differences were found in cluster TMB scores. We also found that immune-related pathways were enriched in C3.
LUAD subtypes based on immune signatures may aid in the development of novel treatment strategies for LUAD.
免疫检查点阻断（ICB）治疗中基于免疫的亚组分类在肺腺癌（LUAD）中大多尚无定论。
首先，基于来自癌症基因组图谱（TCGA）数据库（n = 504）的29种免疫特征的免疫基因组分析，使用单样本基因集富集分析（ssGSEA）和K均值算法来识别LUAD队列中基于免疫的亚型。其次，我们使用生物信息学分析来检验基于免疫的亚型的预后和预测价值。对LUAD进行生存分析和额外的COX比例风险回归分析。然后，分析三种亚型的免疫评分、肿瘤浸润免疫细胞（TIICs）和免疫检查点表达。随后对三种基于免疫的亚型之间差异表达基因（DEG）的基因本体（GO）和京都基因与基因组百科全书（KEGG）进行功能富集途径分析。
已为LUAD鉴定出总共三种具有不同免疫特征的基于免疫的亚型，并分别命名为簇1（C1）、簇2（C2）和簇3（C3）。C3组患者的基质、免疫和ESTIMATE评分较高，而C1组患者则相反。C1组患者的M0巨噬细胞富集且树突状细胞活化，而C3组肿瘤中CD8 T细胞富集、CD4记忆T细胞活化且M1巨噬细胞富集。C3组比其他亚型具有更高的免疫细胞浸润和更好的生存预后。此外，C3组患者的免疫检查点蛋白如PD-L1、PD1、CTLA4、LAG3、IDO1和HAVCR2的表达水平更高。簇TMB评分未发现显著差异。我们还发现免疫相关途径在C3组中富集。
基于免疫特征的LUAD亚型可能有助于开发LUAD的新型治疗策略。
