Hui Lian, Yang Ning, Yang Huijun, Guo Xing, Jang Xuejun
Department of Otolaryngology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
Oncol Rep. 2015 Nov;34(5):2627-35. doi: 10.3892/or.2015.4230. Epub 2015 Aug 27.
The aim of this study was to identify biomarkers with a tumor stage-dependent expression manner and explore the regulatory mechanisms of laryngeal squamous cell carcinoma (LSCC) progression. Microarray data GSE59102 was used for differential analysis using a limma package. Enrichment analyses were performed for the differentially expressed genes (DEGs) between tumor tissues and normal tissues at different stages. A co-expressed network involving the overlapped DEGs in two stages was established based on Pearson's correlation coefficients. Furthermore, for the tumor stage‑dependent expressed DEGs, a protein‑protein interaction (PPI) network was constructed by mapping the genes using the STRING database. Transcription factors (TFs), oncogenes and tumor‑associated genes (TSGs) among the DEGs were predicted, following a search of the TRANSFAC, tumor-associated gene (TAG) and TSG databases. The CDT database was used to identify LSCC‑associated genes. In total, 696 DEGs from early stage and control samples and 622 DEGs from advanced sttage and control samples were selected, which were mainly enriched in the cell cycle pathway. In the co-expressed network, BUB1, TTK, E2F1 and CEP55 were prominent, with E2F1 being predicted as a TSG and CEP55 as an oncogene. The HOX family members were predicted as TFs. MMP1, MMP9, MMP3 and PLAU were the most evident nodes in the PPI network, where MMP3 was connected with MMP1. The ADH family was correlated with LSCC. Several biomarkers with tumor stage-dependent expression were identified including MMP1, MMP3, MMP9, PLAU and ADHs. Additionally, the dysregulated cell cycle pathway involving BUB1, TTK, E2F1 and CEP55, and the mediation of MMP1 by MMP3 as well as the predicted TF HOX, may all play significant roles in LSCC progression.
本研究的目的是鉴定具有肿瘤分期依赖性表达方式的生物标志物，并探索喉鳞状细胞癌（LSCC）进展的调控机制。使用limma软件包对微阵列数据GSE59102进行差异分析。对不同阶段肿瘤组织和正常组织之间的差异表达基因（DEGs）进行富集分析。基于皮尔逊相关系数建立了一个涉及两个阶段重叠DEGs的共表达网络。此外，对于肿瘤分期依赖性表达的DEGs，使用STRING数据库通过映射基因构建了蛋白质-蛋白质相互作用（PPI）网络。在搜索TRANSFAC、肿瘤相关基因（TAG）和TSG数据库后，预测了DEGs中的转录因子（TFs）、癌基因和肿瘤相关基因（TSGs）。使用CDT数据库鉴定LSCC相关基因。总共从早期样本和对照样本中筛选出696个DEGs，从晚期样本和对照样本中筛选出622个DEGs，这些基因主要富集在细胞周期途径中。在共表达网络中，BUB1、TTK、E2F1和CEP55较为突出，其中E2F1被预测为TSG，CEP55被预测为癌基因。HOX家族成员被预测为TFs。MMP1、MMP9、MMP3和PLAU是PPI网络中最明显的节点，其中MMP3与MMP1相连。ADH家族与LSCC相关。鉴定出了几种具有肿瘤分期依赖性表达的生物标志物，包括MMP1、MMP3、MMP9、PLAU和ADHs。此外，涉及BUB1、TTK、E2F1和CEP55的细胞周期途径失调，MMP3对MMP1的调节以及预测的TF HOX，可能在LSCC进展中都发挥重要作用。
