Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Medical Oncology, West China School of Public Health, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Biosci Rep. 2021 Jun 25;41(6). doi: 10.1042/BSR20204370.
Accumulating evidence has demonstrated that gene alterations play a crucial role in LUAD development, progression, and prognosis. The present study aimed to identify the hub genes associated with LUAD. In the present study, we used TCGA database to screen the hub genes. Then, we validated the results by GEO datasets. Finally, we used cBioPortal, UALCAN, qRT-PCR, HPA database, TCGA database, and Kaplan-Meier plotter database to estimate the gene mutation, gene transcription, protein expression, clinical features of hub genes in patients with LUAD. A total of 5930 DEGs were screened out in TCGA database. Enrichment analysis revealed that DEGs were involved in the transcriptional misregulation in cancer, viral carcinogenesis, cAMP signaling pathway, calcium signaling pathway, and ECM-receptor interaction. The combining results of MCODE and CytoHubba showed that ADCY8, ADRB2, CALCA, GCG, GNGT1, and NPSR1 were hub genes. Then, we verified the above results by GSE118370, GSE136043, and GSE140797 datasets. Compared with normal lung tissues, the expression levels of ADCY8 and ADRB2 were lower in LUAD tissues, but the expression levels of CALCA, GCG, GNGT1, and NPSR1 were higher. In the prognosis analyses, the low expression of ADCY8 and ADRB2 and the high expression of CALCA, GCG, GNGT1, and NPSR1 were correlated with poor OS and poor PFS. The significant differences in the relationship of the expression of 6 hub genes and clinical features were observed. In conclusion, 6 hub genes will not only contribute to elucidating the pathogenesis of LUAD and may be potential therapeutic targets for LUAD.
越来越多的证据表明，基因改变在 LUAD 的发生、发展和预后中起着关键作用。本研究旨在鉴定与 LUAD 相关的枢纽基因。在本研究中，我们使用 TCGA 数据库筛选枢纽基因。然后，我们通过 GEO 数据集验证结果。最后，我们使用 cBioPortal、UALCAN、qRT-PCR、HPA 数据库、TCGA 数据库和 Kaplan-Meier plotter 数据库来评估 LUAD 患者的基因突变、基因转录、蛋白质表达和临床特征。在 TCGA 数据库中筛选出 5930 个差异表达基因。富集分析显示，差异表达基因参与了癌症转录失调、病毒致癌作用、cAMP 信号通路、钙信号通路和 ECM-受体相互作用。MCODE 和 CytoHubba 的联合结果表明，ADCY8、ADRB2、CALCA、GCG、GNGT1 和 NPSR1 是枢纽基因。然后，我们通过 GSE118370、GSE136043 和 GSE140797 数据集验证了上述结果。与正常肺组织相比，ADCY8 和 ADRB2 在 LUAD 组织中的表达水平较低，而 CALCA、GCG、GNGT1 和 NPSR1 的表达水平较高。在预后分析中，ADCY8 和 ADRB2 表达水平低，CALCA、GCG、GNGT1 和 NPSR1 表达水平高与 OS 和 PFS 不良相关。6 个枢纽基因的表达与临床特征的关系存在显著差异。综上所述，这 6 个枢纽基因不仅有助于阐明 LUAD 的发病机制，而且可能成为 LUAD 的潜在治疗靶点。
