本研究旨在鉴定参与多原发性肺癌发生发展的关键基因。进行差异表达分析，然后比较多发性和单发性原发性肺腺癌之间22种免疫细胞类型的浸润水平。鉴定了两种类型肺腺癌之间不同比例的上皮细胞的标记基因。鉴定了标记基因和差异表达基因之间的共同基因。最后测试关键基因对体外增殖、迁移和形态的影响。多发性骨髓瘤患者辅助滤泡T细胞、静息NK细胞、活化NK细胞、M2巨噬细胞和静息肥大细胞的浸润水平较高。与单发原发性肺腺癌的患者相比。共鉴定出1553个上皮细胞差异表达基因和4414个标记基因。对 164 个所得基因进行逻辑回归分析。巨噬细胞迁移抑制因子表达与多原发性肺腺癌的发生呈正相关。此外，其信号通路是上皮细胞与多发和单发原发性肺腺癌细胞之间的关键通路，并且在肺腺癌细胞中表达上调。它还增加肺癌标志物NES和CA125的表达，诱导肺泡II型上皮细胞形态变化，促进其增殖、迁移和侵袭。多发性和单发性原发性肺腺癌具有不同的肿瘤免疫微环境和迁移抑制因子可能是多原发性肺腺癌发生的关键因素。© 2023 作者。约翰·威利出版的《临床与转化医学》

This study aimed to identify the key genes involved in the development of multiple primary lung cancers.Differential expression analysis was performed, followed by comparing the infiltration levels of 22 immune cell types between multiple and single primary lung adenocarcinomas. Marker genes for epithelial cells with different proportions between the two types of lung adenocarcinomas were identified. The common genes between the marker genes and differentially expressed genes were identified. Finally, the effects of the key genes were tested on the in vitro proliferation, migration and morphology.The infiltration levels of helper follicular T cells, resting NK cells, activated NK cells, M2 macrophages and resting mast cells were higher in the patients with multiple than in those with single primary lung adenocarcinomas. A total of 1553 differentially expressed genes and 4414 marker genes of epithelial cells were identified. Logistic regression analysis was performed on the 164 resulting genes. The macrophage migration inhibitory factor expression was positively associated with the occurrence of multiple primary lung adenocarcinomas. Moreover, its signalling pathway was the key pathway among the epithelial cells and multiple and single primary lung adenocarcinoma cells, and it was upregulated in lung adenocarcinoma cells. It also increased the expression of lung cancer markers, including NES and CA125, induced morphological changes in alveolar epithelial type II cells, and promoted their proliferation, migration and invasion.Multiple and single primary lung adenocarcinomas have different tumour immune microenvironments, and migration inhibitory factor may be a key factor in the occurrence of multiple primary lung adenocarcinomas.© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.