Prognostic Value of BIRC5 in Lung Adenocarcinoma Lacking EGFR, KRAS, and ALK Mutations by Integrated Bioinformatics Analysis
Prognostic Value of BIRC5 in Lung Adenocarcinoma Lacking EGFR, KRAS, and ALK Mutations by Integrated Bioinformatics Analysis
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通过综合生物信息学分析 BIRC5 在缺乏 EGFR、KRAS 和 ALK 突变的肺腺癌中的预后价值
DOI：
10.1155/2019/5451290
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发表时间：
2019-01-01
期刊：
影响因子：
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通讯作者：
Li, Yan
中科院分区：
文献类型：
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作者：
Cao, Yajuan;Zhu, Weikang;Li, Yan
目的探讨杆状病毒IAP重复序列5（Baculoviral IAP repeat containing 5，BIRC 5）在EGFR、KRAS和ALK突变缺失的肺腺癌（triple-negative adenocarcinoma，TN）中的预后意义。方法从基因表达数据库（GEO）中获取基因表达谱。通过GeneSpring GX进行差异表达基因（DEG）的鉴定。基因集合富集分析（GSEA）用于基因本体功能和途径富集分析。蛋白质相互作用网络由Cytoscape构建。通过MCODE和cytoHubba插件从网络中提取hub基因。然后，使用BIRC 5作为候选物，分别通过Kaplan-Meier RT-PCR和癌症基因组图谱（TCGA）数据库验证其在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了BIRC 5的作用机制。结果共鉴定出38个上调基因和121个下调基因。提取了9个hub基因。其中BIRC 5、MCM 4、CDC 20、KIAA 0101和TRIP 13 5个基因的mRNA表达在TN腺癌中显著上调（P均< 0.05）。值得注意的是，只有BIRC 5的过表达与TN腺癌中不利的总生存期（OS）相关（对数秩P = 0.0037）。BIRC 5高表达组的TN腺癌患者具有显著高的远处转移（P = 0.046）、晚期N分期（P = 0.033）、荷瘤（P = 0.031）和死亡状态（P = 0.003）的风险。BIRC 5及其共表达基因的作用机制可能与细胞周期密切相关。结论BIRC 5在TN腺癌中的过表达与TN腺癌的不良生存率相关。BIRC 5是TN腺癌的潜在预测因子和治疗靶点。
Objective 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). Methods 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. Results 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 P < 0.05). Notably, only the overexpression of BIRC5 was associated with unfavorable overall survival (OS) in TN adenocarcinomas (log rank P = 0.0037). TN adenocarcinoma patients in the BIRC5 high-expression group suffered from a significantly high risk of distant metastasis (P = 0.046), advanced N stage (P = 0.033), and tumor-bearing (P = 0.031) and deceased status (P = 0.003). The mechanism of BIRC5 and coexpressed genes may be linked closely with the cell cycle. Conclusion Overexpressed in tumors, BIRC5 is associated with unfavorable overall survival in TN adenocarcinomas. BIRC5 is a potential predictor and therapeutic target in TN adenocarcinomas.