Nantong Key Laboratory of Translational Medicine in Cardiothoracic Diseases and Research Institution of Translational Medicine in Cardiothoracic Diseases, Affiliated Hospital of Nantong University, Nantong, China.
Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China.
Thorac Cancer. 2022 Jun;13(12):1837-1849. doi: 10.1111/1759-7714.14466. Epub 2022 May 13.
Lung adenocarcinoma (LUAD) is one of the tumor-related diseases with high morbidity worldwide. Epigenetic modifications such as DNA methylation changes may involve in tumorigenesis. This study aimed to explore new biomarkers that have prognostic significance of LUAD.
First, we downloaded the gene expression and methylation data set from Gene Expression Omnibus. R software was then used to identify abnormally methylated differentially expressed genes (MDEGs). Next, R package Cluster Profiler was used to analyze the enrichment and pathway of the MDEGs. Analysis using STRING revealed the protein-protein interaction network. The result was then visualized by Cytoscape and obtained 10 hub genes. Afterward, they were further verified by The Cancer Genome Atlas to select candidate genes. Moreover, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to verify the expression and prognostic value of candidate genes in LUAD patients.
The results showed that the expressions of ADCY5 and PRKCB are indeed related to LUAD. The clinical relevance to PRKCB was confirmed by its clinical correlation analysis. Gene set enrichment analysis (GSEA) and tumor immune estimation resource (TIMER) tumor immune correlations showed that PRKCB is involved in the cancer-related Kyoto Encyclopedia of Genes and Genomes pathway and is involved in immune infiltration. It was also verified by qRT-PCR and immunohistochemistry that PRKCB was lowly expressed in LUAD patients and correlated with prognosis.
PRKCB is relevant to prognosis of LUAD through methylation and immune infiltration.
肺腺癌(LUAD)是全球发病率较高的肿瘤相关疾病之一。表观遗传修饰,如 DNA 甲基化改变,可能与肿瘤发生有关。本研究旨在探索具有 LUAD 预后意义的新生物标志物。
首先,我们从基因表达综合数据库(GEO)中下载基因表达和甲基化数据集。然后,R 软件用于识别异常甲基化的差异表达基因(MDEGs)。接下来,使用 R 包 Cluster Profiler 分析 MDEGs 的富集和通路。使用 STRING 进行的分析揭示了蛋白质-蛋白质相互作用网络。结果通过 Cytoscape 可视化,并获得 10 个枢纽基因。然后,通过癌症基因组图谱(TCGA)进一步验证,以选择候选基因。此外,采用实时定量聚合酶链反应(qRT-PCR)和免疫组织化学法验证候选基因在 LUAD 患者中的表达和预后价值。
结果表明,ADCY5 和 PRKCB 的表达确实与 LUAD 相关。通过其临床相关性分析,证实了 PRKCB 与临床的相关性。基因集富集分析(GSEA)和肿瘤免疫估计资源(TIMER)肿瘤免疫相关性表明,PRKCB 参与癌症相关京都基因与基因组百科全书通路,并参与免疫浸润。qRT-PCR 和免疫组织化学法也验证了 PRKCB 在 LUAD 患者中低表达,并与预后相关。
PRKCB 通过甲基化和免疫浸润与 LUAD 的预后相关。