探讨肺腺癌的潜在关键基因及其在诊断与预后方面的价值。

利用生物信息学方法从开放基因芯片数据库获取肺腺癌表达的数据集(GSE10072，GSE32867，GSE43458)，采用在线工具GEO2R筛选出在肺腺癌组织与正常组织中具有差异表达的基因。对筛选出的基因进行GO功能富集及KEGG信号通路分析，同时应用STRING数据库和Cytoscape软件构建相关基因编码的蛋白间相互作用网络图，并筛选出连接度较高的前8个基因，同时利用R语言分析肺腺癌中相关基因的表达情况，及其与预后、肿瘤微环境的关系。

从3个数据集筛选出存在差异表达的基因240个，取蛋白间相互作用连接度最高的前8个基因作为关键基因，GO功能富集分析结果显示生物学过程主要富集在细胞黏附、耐药性等方面；细胞学成分主要位于细胞质、细胞膜、细胞外泌体等；分子功能主要与钙离子结合的过程相关，KEGG信号通路分析主要集中于PI3K/AKT/MAPK信号通路。8个关键基因在肺腺癌与正常组织中均呈差异表达(均P<0.05)，其中，CDC20、TIMP1、CCNB2、KIAA0101、TOP2A高表达组的患者预后较低表达组的患者预后更差，均差异有统计学意义(均P<0.01)。8个关键基因均在一定程度上影响其周围的免疫浸润，其中CCNB2(r＝0.43)、CDC20(r＝0.46)、GNG11(r＝-0.11)、KIAA0101(r＝0.32)、TIMP1(r＝-0.10)、TOP2A(r＝0.43)的表达水平与其肿瘤突变负荷均存在相关性(均P<0.05)。

在肺腺癌患者中存在着差异表达的基因，部分关键基因可能参与了肺腺癌细胞发生、发展、转移侵袭、耐药等生物学相关功能，有望成为肺腺癌的个体化诊断、预后评估的潜在标志物。

To explore the potential key genes of lung adenocarcinoma (LUAD) and their diagnostic and prognostic value.

We downloaded the ChIP data (GSE10072, GSE32867, GSE43458) from the GEO database, and analyzed these data using online tool GEO2R to obtain the differentially expressed genes (DEGs) between cancer tissues and normal tissues. These DEGs were analyzed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We used the STRING database to build a protein-protein interaction (PPI) network, then ranked the genes by the descending order of the links between proteins, finally the top 8 genes were considered as the key genes. The expression profile, prognosis, and the tumor mutation burden (TMB) were analyzed using R (4.0.0).

A total of 240 genes differentially expressed among three ChIP data were screened out, and the GO outcome showed that these DEGs mainly concentrated in cell adhesion and drug resistance. Cytological components were mainly located in cytoplasm, cell membrane, and extracellular exosome. The molecular function was enriched in calcium ion binding. KEGG signaling pathway analysis showed that the DEGs were mainly involved in PI3K/AKT/MAPK pathway. The 8 genes all expressed differentially between tumor and normal tissues, and patients with higher expression of CDC20, TIMP1, CCNB2, KIAA0101 and TOP2A had worse overall surviver (OS) than the patients with lower expression (all P<0.01). What's more, the key genes also affect the immune infiltration in the tumor, and the expression levels of CCNB2 (r=0.43), CDC20(r=0.46), GNG11(r=-0.11), KIAA0101(r=0.32), TIMP1(r=-0.10), TOP2A(r=0.43) were associated with the TMB (all P<0.05).

There are DEGs in patients with LUAD, a part of these key genes may be involved in the occurrence, development, metastasis, invasion, and drug resistance of LUAD cells and other biological functions, and are expected to become potential markers for individualized diagnosis and prognostic evaluation of LUAD.