Huang Ping, Cao Kejian, Zhao Heng
Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, NO.241 Huaihaixi Road, Shanghai, 200030, People's Republic of China.
Pathol Oncol Res. 2014 Oct;20(4):853-8. doi: 10.1007/s12253-014-9764-z. Epub 2014 May 26.
Biomarker discovery is of great importance in diagnosis and treatment of diseases. In present study, a number of differentially expressed genes (DEGs) were identified for lung adenocarcinoma via comparative analysis of gene expression data. A gene expression core signature was generated for four types of lung adenocarcinoma (EGFR-mutated, KRAS-mutated, ALK-mutated and triple-negative adenocarcinoma). Functional enrichment analysis with DAVID tools revealed that up-regulated genes were mainly associated with cell cycle while down-regulated genes were mainly involved in vasculature development and cell adhesion. Then it was used to retrieve relevant small molecule drugs with Connectivity map and trichostatin A was predicted to be the top candidate drug for treatment of lung cancer. Network clustering was performed with MCL in cytoscape to identify sub-networks and several hub genes were obtained: CDC25C, ICT1, TK1 and EZH2. These genes play important roles in the progression of lung cancer and some have been suggested as potential biomarkers. Therefore, our findings are beneficial in deepening the understandings about the pathogenesis and providing directions for future researches.
生物标志物的发现对于疾病的诊断和治疗至关重要。在本研究中，通过对基因表达数据的比较分析，鉴定出了一些肺腺癌的差异表达基因（DEGs）。针对四种类型的肺腺癌（表皮生长因子受体（EGFR）突变型、 Kirsten 大鼠肉瘤病毒癌基因（KRAS）突变型、间变性淋巴瘤激酶（ALK）突变型和三阴性腺癌）生成了一个基因表达核心特征。使用DAVID工具进行功能富集分析表明，上调基因主要与细胞周期相关，而下调基因主要参与血管系统发育和细胞黏附。然后利用连通图检索相关小分子药物，预测曲古抑菌素A是治疗肺癌的最佳候选药物。在Cytoscape中使用马尔可夫聚类算法（MCL）进行网络聚类以识别子网，并获得了几个枢纽基因：细胞分裂周期蛋白25C（CDC25C）、ICT1、胸苷激酶1（TK1）和EZH2。这些基因在肺癌进展中起重要作用，一些已被建议作为潜在的生物标志物。因此，我们的研究结果有助于加深对发病机制的理解，并为未来的研究提供方向。
