Table_3_A signature-based classification of lung adenocarcinoma that stratifies tumor immunity.xlsx

BackgroundImmune-related subgroup classification in immune checkpoint blockade (ICB) therapy is largely inconclusive in lung adenocarcinoma (LUAD).
Materials and methodsFirst, 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.
ResultA 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.
ConclusionLUAD subtypes based on immune signatures may aid in the development of novel treatment strategies for LUAD.

背景：免疫检查点阻断（immune checkpoint blockade, ICB）治疗中的免疫相关亚型分类在肺腺癌（LUAD）中尚无定论。
材料与方法：首先，基于癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据库中504例肺腺癌队列的29个免疫特征免疫基因组谱，采用单样本基因集富集分析（single-sample Gene Set Enrichment Analysis, ssGSEA）与K-means算法鉴定免疫相关亚型。其次，通过生物信息学分析评估免疫相关亚型的预后与预测价值：对肺腺癌队列开展生存分析及额外的COX比例风险回归分析；随后分析三种亚型的免疫评分、肿瘤浸润免疫细胞（tumor-infiltrating immune cells, TIICs）及免疫检查点表达水平；进而对三种免疫亚型间的差异表达基因（differentially expressed genes, DEGs）进行基因本体（Gene Ontology, GO）与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）功能富集通路分析。
结果：本研究共鉴定出三种具有独特免疫特征的肺腺癌免疫相关亚型，分别命名为簇1（C1）、簇2（C2）与簇3（C3）。C3组患者的基质评分、免疫评分及ESTIMATE评分均更高，而C1组则相反。C1组肿瘤中可见M0型巨噬细胞富集与树突状细胞活化，C3组肿瘤则存在CD8+T细胞富集、CD4+记忆T细胞活化及M1型巨噬细胞浸润。相较于其他亚型，C3组免疫细胞浸润程度更高，生存预后更佳。此外，C3组的PD-L1、PD1、CTLA4、LAG3、IDO1及HAVCR2等免疫检查点蛋白表达水平更高。三组的肿瘤突变负荷（TMB）评分无显著差异。本研究还发现免疫相关通路在C3组中显著富集。
结论：基于免疫特征的肺腺癌亚型分类，可为肺腺癌的新型治疗策略开发提供参考。