Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Translational Medicine Research Center, North Sichuan Medical College, Nanchong, China.
J Cell Physiol. 2019 Dec;234(12):22742-22752. doi: 10.1002/jcp.28839. Epub 2019 May 24.
Non-small-cell lung cancer (NSCLC) is one of the main causes of death induced by cancer globally. However, the molecular aberrations in NSCLC patients remain unclearly. In the present study, four messenger RNA microarray datasets (GSE18842, GSE40275, GSE43458, and GSE102287) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between NSCLC tissues and adjacent lung tissues were obtained from GEO2R and the overlapping DEGs were identified. Moreover, functional and pathway enrichment were performed by Funrich, while the protein-protein interaction (PPI) network construction were obtained from STRING and hub genes were visualized and identified by Cytoscape software. Furthermore, validation, overall survival (OS) and tumor staging analysis of selected hub genes were performed by GEPIA. A total of 367 DEGs (95 upregulated and 272 downregulated) were obtained through gene integration analysis. The PPI network consisted of 94 nodes and 1036 edges in the upregulated DEGs and 272 nodes and 464 edges in the downregulated DEGs, respectively. The PPI network identified 46 upregulated and 27 downregulated hub genes among the DEGs, and six (such as CENPE, NCAPH, MYH11, LRRK2, HSD17B6, and A2M) of that have not been identified to be associated with NSCLC so far. Moreover, the expression differences of the mentioned hub genes were consistent with that in lung adenocarcinoma and lung squamous cell carcinoma in the TCGA database. Further analysis showed that all the six hub genes were associated with tumor staging except MYH11, while only the upregulated DEG CENPE was associated with the worse OS of patients with NSCLC. In conclusion, the current study showed that CENPE, NCAPH, MYH11, LRRK2, HSD17B6, and A2M might be the key genes contributed to tumorigenesis or tumor progression in NSCLC, further functional study is needed to explore the involved mechanisms.
非小细胞肺癌 (NSCLC) 是全球癌症死亡的主要原因之一。然而，NSCLC 患者的分子异常仍不清楚。在本研究中，从基因表达综合数据库 (GEO) 下载了四个信使 RNA 微阵列数据集 (GSE18842、GSE40275、GSE43458 和 GSE102287)。从 GEO2R 获得 NSCLC 组织与相邻肺组织之间的差异表达基因 (DEGs)，并识别重叠的 DEGs。此外，通过 Funrich 进行功能和途径富集，通过 STRING 获得蛋白质-蛋白质相互作用 (PPI) 网络构建，通过 Cytoscape 软件可视化和识别枢纽基因。进一步通过 GEPIA 验证、总生存期 (OS) 和肿瘤分期分析选定的枢纽基因。通过基因整合分析共获得 367 个 DEGs(95 个上调和 272 个下调)。上调 DEGs 的 PPI 网络包含 94 个节点和 1036 个边，下调 DEGs 的 PPI 网络包含 272 个节点和 464 个边。PPI 网络在 DEGs 中识别出 46 个上调和 27 个下调的枢纽基因，其中 6 个 (如 CENPE、NCAPH、MYH11、LRRK2、HSD17B6 和 A2M) 尚未被确定与 NSCLC 有关。此外，在 TCGA 数据库中，所述枢纽基因的表达差异与肺腺癌和肺鳞癌一致。进一步分析表明，除 MYH11 外，所有 6 个枢纽基因都与肿瘤分期有关，而只有上调的 DEG CENPE 与 NSCLC 患者的 OS 较差有关。总之，本研究表明 CENPE、NCAPH、MYH11、LRRK2、HSD17B6 和 A2M 可能是 NSCLC 肿瘤发生或肿瘤进展的关键基因，需要进一步的功能研究来探讨其涉及的机制。
