The Key Laboratory of Pathobiology, Ministry of Education, Department of Pathology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China.
Pediatric Department of Respiration II, The First Hospital of Jilin University, Changchun, Jilin, China.
Biomed Res Int. 2022 Jul 30;2022:7848771. doi: 10.1155/2022/7848771. eCollection 2022.
More than 40% of lung cancers are lung adenocarcinoma (LUAD) worldwide. However, the prognosis of LUAD is poor for the lack of effective treatment methods. Our study identified PLK1 as a novel prognosis biomarker and treatment target for LUAD. Based on the Cancer Genome Atlas (TCGA) database, differentially expressed genes (DEGs) from 551 LUAD cases were analyzed for the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. To explore the biological pathways and the tumor-infiltrating immune cells (TICs) using gene set variation analysis (GSVA) and the CIBERSORT, as well as to analyze DEGs, a protein-protein interaction (PPI) network and Cox regression analysis were performed. Validation of DEGs was achieved through quantitative real-time PCR (qPCR) and immunoblotting. DEGs associated with the cell cycle were sorted out. Cell cycle scores were positively correlated with age, clinical stages, and metastasis and negatively correlated with overall survival of LUAD patients. PPI and Cox analyses showed that PLK1 could be a prognostic factor for LUAD patients. CIBERSORT analysis revealed a positive correlation between the transcription level of PLK1 and the function of CD8+ and activated memory CD4+ T cells, as well as a negative correlation with activated natural killer cells. Furthermore, PLK1 overexpression increased immune cytotoxicity, as measured by the cytolytic activity score, IFN- score, and IFN- level. There is a strong correlation between PLK1 and key features of TICs, indicating its potential as a promising prognostic biomarker for LUAD.
全世界超过 40%的肺癌是肺腺癌（LUAD）。然而，由于缺乏有效的治疗方法，LUAD 的预后较差。我们的研究确定 PLK1 是 LUAD 的一个新的预后生物标志物和治疗靶点。基于癌症基因组图谱（TCGA）数据库，分析了 551 例 LUAD 病例的差异表达基因（DEGs）进行京都基因与基因组百科全书（KEGG）富集分析。使用基因集变异分析（GSVA）和 CIBERSORT 探索生物学途径和肿瘤浸润免疫细胞（TICs），并分析 DEGs、蛋白质-蛋白质相互作用（PPI）网络和 Cox 回归分析。通过定量实时 PCR（qPCR）和免疫印迹验证 DEGs。对与细胞周期相关的 DEGs 进行了分类。细胞周期评分与 LUAD 患者的年龄、临床分期、转移呈正相关，与总生存时间呈负相关。PPI 和 Cox 分析表明，PLK1 可能是 LUAD 患者的预后因素。CIBERSORT 分析显示，PLK1 的转录水平与 CD8+和激活的记忆 CD4+T 细胞的功能呈正相关，与激活的自然杀伤细胞呈负相关。此外，PLK1 的过表达增加了免疫细胞毒性，通过细胞溶解活性评分、IFN-评分和 IFN-水平来衡量。PLK1 与 TICs 的关键特征之间存在很强的相关性，表明其作为 LUAD 有前途的预后生物标志物的潜力。
