Department of Otolaryngology-Head Neck Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
Department of Respiratory Medicine, The First Hospital of Changsha, Changsha 410000, Hunan Province, China.
Biosci Rep. 2021 Jan 29;41(1). doi: 10.1042/BSR20203973.
Lung adenocarcinoma (LUAD) is the most frequent histological type of lung cancer, and its incidence has displayed an upward trend in recent years. Nevertheless, little is known regarding effective biomarkers for LUAD.
The robust rank aggregation method was used to mine differentially expressed genes (DEGs) from the gene expression omnibus (GEO) datasets. The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to extract hub genes from the protein-protein interaction (PPI) network. The expression of the hub genes was validated using expression profiles from TCGA and Oncomine databases and was verified by real-time quantitative PCR (qRT-PCR). The module and survival analyses of the hub genes were determined using Cytoscape and Kaplan-Meier curves. The function of KIF4A as a hub gene was investigated in LUAD cell lines.
The PPI analysis identified seven DEGs including BIRC5, DLGAP5, CENPF, KIF4A, TOP2A, AURKA, and CCNA2, which were significantly upregulated in Oncomine and TCGA LUAD datasets, and were verified by qRT-PCR in our clinical samples. We determined the overall and disease-free survival analysis of the seven hub genes using GEPIA. We further found that CENPF, DLGAP5, and KIF4A expressions were positively correlated with clinical stage. In LUAD cell lines, proliferation and migration were inhibited and apoptosis was promoted by knocking down KIF4A expression.
We have identified new DEGs and functional pathways involved in LUAD. KIF4A, as a hub gene, promoted the progression of LUAD and might represent a potential therapeutic target for molecular cancer therapy.
肺腺癌（LUAD）是最常见的肺癌组织学类型，近年来其发病率呈上升趋势。然而，对于 LUAD 有效的生物标志物知之甚少。
使用稳健秩聚合方法从基因表达综合数据库（GEO）数据集中挖掘差异表达基因（DEGs）。使用搜索工具检索相互作用基因（STRING）数据库从蛋白质-蛋白质相互作用（PPI）网络中提取枢纽基因。使用 TCGA 和 Oncomine 数据库的表达谱验证枢纽基因的表达，并通过实时定量 PCR（qRT-PCR）进行验证。使用 Cytoscape 和 Kaplan-Meier 曲线确定枢纽基因的模块和生存分析。使用 LUAD 细胞系研究 KIF4A 作为枢纽基因的功能。
PPI 分析确定了 7 个 DEGs，包括 BIRC5、DLGAP5、CENPF、KIF4A、TOP2A、AURKA 和 CCNA2，这些基因在 Oncomine 和 TCGA LUAD 数据集均显著上调，并通过 qRT-PCR 在我们的临床样本中得到验证。我们使用 GEPIA 对这 7 个枢纽基因进行了总生存期和无病生存期分析。我们进一步发现 CENPF、DLGAP5 和 KIF4A 的表达与临床分期呈正相关。在 LUAD 细胞系中，敲低 KIF4A 表达可抑制增殖和迁移，促进凋亡。
我们已经确定了新的与 LUAD 相关的差异表达基因和功能途径。KIF4A 作为一个枢纽基因，促进了 LUAD 的进展，可能代表了分子癌症治疗的潜在治疗靶点。
