Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
Dis Markers. 2019 Apr 9;2019:5451290. doi: 10.1155/2019/5451290. eCollection 2019.
This study was aimed at investigating the prognostic significance of Baculoviral IAP repeat containing 5 (BIRC5) in lung adenocarcinoma (LAD) lacking EGFR, KRAS, and ALK mutations (triple-negative (TN) adenocarcinomas).
The gene expression profiles were obtained from Gene Expression Omnibus (GEO). The identification of the differentially expressed genes (DEGs) was performed by GeneSpring GX. Gene set enrichment analysis (GSEA) was used to execute gene ontology function and pathway enrichment analysis. The protein interaction network was constructed by Cytoscape. The hub genes were extracted by MCODE and cytoHubba plugin from the network. Then, using BIRC5 as a candidate, the prognostic value in LAD and TN adenocarcinomas was verified by the Kaplan-Meier plotter and The Cancer Genome Atlas (TCGA) database, respectively. Finally, the mechanism of BIRC5 was predicted by a coexpressed network and enrichment analysis.
A total of 38 upregulated genes and 121 downregulated genes were identified. 9 hub genes were extracted. Among them, the mRNA expression of 5 genes, namely, BIRC5, MCM4, CDC20, KIAA0101, and TRIP13, were significantly upregulated among TN adenocarcinomas (all < 0.05). Notably, only the overexpression of BIRC5 was associated with unfavorable overall survival (OS) in TN adenocarcinomas (log rank = 0.0037). TN adenocarcinoma patients in the BIRC5 high-expression group suffered from a significantly high risk of distant metastasis ( = 0.046), advanced N stage ( = 0.033), and tumor-bearing ( = 0.031) and deceased status ( = 0.003). The mechanism of BIRC5 and coexpressed genes may be linked closely with the cell cycle.
Overexpressed in tumors, BIRC5 is associated with unfavorable overall survival in TN adenocarcinomas. BIRC5 is a potential predictor and therapeutic target in TN adenocarcinomas.
本研究旨在探讨在缺乏表皮生长因子受体（EGFR）、KRAS 和间变性淋巴瘤激酶（ALK）突变的肺腺癌（LAD）中，杆状病毒 IAP 重复包含 5（BIRC5）的预后意义。
从基因表达综合数据库（GEO）获取基因表达谱。使用 GeneSpring GX 识别差异表达基因（DEGs）。采用基因集富集分析（GSEA）进行基因本体功能和通路富集分析。使用 Cytoscape 构建蛋白质相互作用网络。通过 MCODE 和 cytoHubba 插件从网络中提取关键基因。然后，以 BIRC5 为候选物，通过 Kaplan-Meier 绘图器和癌症基因组图谱（TCGA）数据库分别验证 LAD 和 TN 腺癌中的预后价值。最后，通过共表达网络和富集分析预测 BIRC5 的作用机制。
共鉴定出 38 个上调基因和 121 个下调基因。提取了 9 个关键基因。其中，5 个基因（BIRC5、MCM4、CDC20、KIAA0101 和 TRIP13）的 mRNA 表达在 TN 腺癌中显著上调（均<0.05）。值得注意的是，仅 BIRC5 的过表达与 TN 腺癌患者的不良总生存期（OS）相关（对数秩检验=0.0037）。BIRC5 高表达组的 TN 腺癌患者发生远处转移的风险显著升高（=0.046）、N 期较晚（=0.033）、肿瘤负荷较大（=0.031）和死亡状态（=0.003）。BIRC5 及其共表达基因的作用机制可能与细胞周期密切相关。
BIRC5 在肿瘤中过表达，与 TN 腺癌的不良总生存期相关。BIRC5 是 TN 腺癌潜在的预测因子和治疗靶点。
