Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China.
School of Public Health, Nanchang University, Nanchang, Jiangxi, 330006, China.
Biosci Rep. 2020 Apr 30;40(4). doi: 10.1042/BSR20200295.
Lung adenocarcinoma (LUAD) remains the leading cause of cancer-related deaths worldwide. Increasing evidence suggests that circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) can regulate target gene expression and participate in tumor genesis and progression. However, hub driving genes and regulators playing a potential role in LUAD progression have not been fully elucidated yet. Based on data from The Cancer Genome Atlas database, 2837 differentially expressed genes, 741 DE-regulators were screened by comparing cancer tissues with paracancerous tissues. Then, 651 hub driving genes were selected by the topological relation of the protein-protein interaction network. Also, the target genes of DE-regulators were identified. Moreover, a key gene set containing 65 genes was obtained from the hub driving genes and target genes intersection. Subsequently, 183 hub regulators were selected based on the analysis of node degree in the ceRNA network. Next, a comprehensive analysis of the subgroups and Wnt, mTOR, and MAPK signaling pathways was conducted to understand enrichment of the subgroups. Survival analysis and a receiver operating characteristic curve analysis were further used to screen for the key genes and regulators. Furthermore, we verified key molecules based on external database, LRRK2, PECAM1, EPAS1, LDB2, and HOXA11-AS showed good results. LRRK2 was further identified as promising biomarker associated with CNV alteration and various immune cells' infiltration levels in LUAD. Overall, the present study provided a novel perspective and insight into hub driving genes and regulators in LUAD, suggesting that the identified signature could serve as an independent prognostic biomarker.
肺腺癌 (LUAD) 仍然是全球癌症相关死亡的主要原因。越来越多的证据表明,环状 RNA (circRNA) 和长非编码 RNA (lncRNA) 可以调节靶基因表达,并参与肿瘤发生和进展。然而,LUAD 进展中潜在发挥作用的关键驱动基因和调控因子尚未被充分阐明。基于癌症基因组图谱数据库的数据,通过比较癌症组织和癌旁组织,筛选出 2837 个差异表达基因和 741 个 DE 调节剂。然后,通过蛋白质-蛋白质相互作用网络的拓扑关系选择 651 个关键驱动基因。同时,确定了 DE 调节剂的靶基因。此外,从关键驱动基因和靶基因的交集获得了一个包含 65 个基因的关键基因集。随后,基于 ceRNA 网络节点度分析,选择了 183 个关键调控因子。接下来,对亚组和 Wnt、mTOR 和 MAPK 信号通路进行综合分析,以了解亚组的富集情况。生存分析和接受者操作特征曲线分析进一步用于筛选关键基因和调控因子。此外,我们基于外部数据库验证了关键分子,LRRK2、PECAM1、EPAS1、LDB2 和 HOXA11-AS 显示出良好的结果。LRRK2 进一步被确定为与 LUAD 中 CNV 改变和各种免疫细胞浸润水平相关的有前途的生物标志物。总之,本研究为 LUAD 中的关键驱动基因和调控因子提供了新的视角和见解,表明所鉴定的特征可以作为独立的预后生物标志物。