Department of Reproductive Genetics, International Peace Maternity and Child Health Hospital, Shanghai Key Laboratory of Embryo Original Diseases, Shanghai Municipal Key Clinical Specialty, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
Biomed Res Int. 2020 Oct 1;2020:8931419. doi: 10.1155/2020/8931419. eCollection 2020.
Lung adenocarcinoma (LUAD) comprises around 40% of all lung cancers, and in about 70% of patients, it has spread locally or systemically when first detected leading to a worse prognosis.
We filtered out differentially expressed genes (DEGs) based on the RNA sequencing data in the Gene Expression Omnibus database and verified and deeply analyzed screened DEGs using a combined bioinformatics approach.
Expressions of 11,143 genes in 694 nontumor lung tissues and LUAD cases from 8 independent laboratories were analyzed; 188 mRNAs were identified as differentially expressed genes (DEGs). A PPI network constructed with 188 DEGs screened out 8 hub DEGs (, , , , , , , and ) which highly interconnected with other nodes. The expression levels of 8 hub genes in LUAD and control were assessed in the Oncomine database, and the results were consistent. The survival curves of 8 hub genes showed that their expressions are significantly related to the prognosis of lung cancer and LUAD patients except for . Since the expression of is nonspecific and highly sensitive, we choose the other 7 hub genes we had verified to do the next analysis. Mutual exclusivity or cooccurrence analysis of 7 hub genes identified a tendency towards cooccurrence between , , and in LUAD. The coexpression profiles of in LUAD were identified, and we found that and coexpressed with CDH5. Immunohistochemistry and RT-PCR analysis showed that higher levels of , , and were expressed in normal lung tissues but a low or undetectable level was found in LUAD tissues.
Taken together, we speculate that , , and played an important role in LUAD.
肺腺癌(LUAD)约占所有肺癌的 40%,约 70%的患者在首次发现时已局部或全身扩散,导致预后较差。
我们根据 GEO 数据库中的 RNA 测序数据筛选差异表达基因(DEGs),并采用综合生物信息学方法对筛选出的 DEGs 进行验证和深入分析。
分析了 8 个独立实验室的 694 例非肿瘤肺组织和 LUAD 病例中 11143 个基因的表达情况,筛选出 188 个差异表达基因(DEGs)。用 188 个 DEGs 构建的 PPI 网络筛选出 8 个核心 DEGs(,, , , , , 和 ),它们与其他节点高度连接。在 Oncomine 数据库中评估了 8 个核心基因在 LUAD 和对照中的表达水平,结果一致。8 个核心基因的生存曲线表明,它们的表达与肺癌和 LUAD 患者的预后显著相关,除了 。由于 的表达非特异性和高度敏感,我们选择了我们已经验证的其他 7 个核心基因进行下一步分析。7 个核心基因的互斥或共发生分析表明,在 LUAD 中存在 、 和 共发生的趋势。鉴定了 LUAD 中 7 个核心基因的共表达谱,发现 与 CDH5 共表达。免疫组化和 RT-PCR 分析显示,在正常肺组织中高表达 、 和 ,而在 LUAD 组织中低表达或检测不到。
综上所述,我们推测 、 和 在 LUAD 中发挥了重要作用。