Kim Kyung Soo, Kang Taewon, Jekarl Dong Wook
Department of Thoracic and Cardiovascular Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Biomedicines. 2024 Mar 12;12(3):628. doi: 10.3390/biomedicines12030628.
The association between immune checkpoint inhibitors (ICIs) and immune gene networks in squamous lung cancer (LUSC) and lung adenocarcinoma (LUAD) was studied. Immune gene networks were constructed using RNA-seq data from the gene expression omnibus (GEO) database. Datasets with more than 10 samples of normal control and tumor tissues were selected; of these, GSE87340, GSE120622, and GSE111907 were suitable for analysis. Gene set enrichment for pathway analysis was performed. For immune gene network construction, 998 unique immune genes were selected from 21 pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG). Gene function annotation was performed based on the KEGG, Gene Ontology, and Reactome databases. Tumor tissues showed decreased coagulation, hematopoiesis, and innate immune pathways, whereas complement- and coagulation-related genes were prominent in the tumor immune gene network. The average numbers of neighbors, clustering coefficients, network diameters, path lengths, densities, and heterogeneities were highest for normal tissue, followed by LUAD and LUSC. Decreased coagulation genes, which were prominent in tumor immune networks, imply functional attenuation. LUAD was deviated from normal tissue, based on network parameters. Tumor tissues showed decreased immune function, and the deviation of LUSC from normal tissue might explain LUSC's better therapeutic response to ICI treatment.
研究了免疫检查点抑制剂（ICI）与肺鳞状细胞癌（LUSC）和肺腺癌（LUAD）中免疫基因网络之间的关联。利用来自基因表达综合数据库（GEO）的RNA测序数据构建免疫基因网络。选择正常对照和肿瘤组织样本数超过10个的数据集；其中，GSE87340、GSE120622和GSE111907适合进行分析。进行基因集富集以进行通路分析。对于免疫基因网络构建，从京都基因与基因组百科全书（KEGG）的21条通路中选择了998个独特的免疫基因。基于KEGG、基因本体论和Reactome数据库进行基因功能注释。肿瘤组织显示凝血、造血和固有免疫通路减少，而补体和凝血相关基因在肿瘤免疫基因网络中突出。正常组织的邻居平均数、聚类系数、网络直径、路径长度、密度和异质性最高，其次是LUAD和LUSC。在肿瘤免疫网络中突出的凝血基因减少意味着功能衰减。基于网络参数，LUAD偏离正常组织。肿瘤组织显示免疫功能降低，LUSC与正常组织的偏差可能解释了LUSC对ICI治疗更好的治疗反应。
