Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
J Transl Med. 2018 Dec 27;16(1):372. doi: 10.1186/s12967-018-1732-z.
Lung adenocarcinoma (LUAD), largely remains a primary cause of cancer-related death worldwide. The molecular mechanisms in LUAD metastasis have not been completely uncovered.
In this study, we identified differentially expressed genes (DEGs), miRNAs (DEMs) and lncRNAs (DELs) underlying metastasis of LUAD from The Cancer Genome Atlas database. Intersection mRNAs were used to perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and co-expression network analysis. In addition, survival analyses of intersection mRNAs were conducted. Finally, intersection mRNAs, miRNAs and lncRNAs were subjected to construct miRNA-mRNA-lncRNA network.
A total of 1015 DEGs, 54 DEMs and 22 DELs were identified in LUAD metastasis and non-metastasis samples. GO and KEGG pathway analysis had proven that the functions of intersection mRNAs were closely related with many important processes in cancer pathogenesis. Among the co-expression interactions network, 22 genes in the co-expression network were over the degree 20. These genes imply that they have connections with many other gene nodes. In addition, 14 target genes (ARHGAP11A, ASPM, HELLS, PRC1, TMPO, ARHGAP30, CD52, IL16, IRF8, P2RY13, PRKCB, PTPRC, SASH3 and TRAF3IP3) were found to be associated with survival in patients with LUAD significantly (log-rank P < 0.05). Two lncRNAs (LOC96610 and ADAM6) acting as ceRNAs were identified based on the miRNA-mRNA-lncRNA network.
Taken together, the results may provide a novel perspective to develop a multiple gene diagnostic tool for LUAD prognosis, which might also provide potential biomarkers or therapeutic targets for LUAD.
肺腺癌（LUAD）在全球范围内仍然是癌症相关死亡的主要原因。LUAD 转移的分子机制尚未完全揭示。
本研究从癌症基因组图谱数据库中鉴定了 LUAD 转移相关的差异表达基因（DEGs）、miRNAs（DEMs）和长链非编码 RNA（DELs）。交集 mRNAs 用于进行基因本体论（GO）、京都基因与基因组百科全书（KEGG）通路和共表达网络分析。此外，还对交集 mRNAs 进行了生存分析。最后，将交集 mRNAs、miRNAs 和 lncRNAs 构建 miRNA-mRNA-lncRNA 网络。
在 LUAD 转移和非转移样本中，共鉴定出 1015 个 DEGs、54 个 DEMs 和 22 个 DELs。GO 和 KEGG 通路分析表明，交集 mRNAs 的功能与癌症发病机制中的许多重要过程密切相关。在共表达相互作用网络中，共表达网络中的 22 个基因的度超过 20。这些基因表明它们与许多其他基因节点有联系。此外，还发现 14 个靶基因（ARHGAP11A、ASPM、HELLS、PRC1、TMPO、ARHGAP30、CD52、IL16、IRF8、P2RY13、PRKCB、PTPRC、SASH3 和 TRAF3IP3）与 LUAD 患者的生存显著相关（对数秩 P<0.05）。基于 miRNA-mRNA-lncRNA 网络，鉴定出两个作为 ceRNA 的 lncRNAs（LOC96610 和 ADAM6）。
综上所述，这些结果可能为 LUAD 预后的多基因诊断工具的开发提供新的视角，也可能为 LUAD 提供潜在的生物标志物或治疗靶点。
