Chen Fang, Shen Congxiang, Wang Xiaoqi, Wang Huigang, Liu Yanhui, Yu Chaosheng, Lv Jieyu, He Jingjing, Wen Zhong
Department of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Department of Otorhinolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Xinjiang Medical University, Xinjiang, China.
Oncotarget. 2017 Jul 22;8(38):63738-63749. doi: 10.18632/oncotarget.19478. eCollection 2017 Sep 8.
Nasopharyngeal carcinoma is a metastatic malignant tumor originating from nasopharyngeal epithelium. Lacking or nonspecific symptoms of patients with early stage nasopharyngeal carcinoma have significantly reduced the accuracy of diagnosing and predicting nasopharyngeal carcinoma development. This study aimed to identify gene signatures of nasopharyngeal carcinoma and uncover potential mechanisms. Two gene expression profiles (GSE12452 and GSE13597) containing 56 nasopharyngeal carcinoma samples and 13 normal control samples were analyzed to identify the differentially expressed genes. In total, 179 up-regulated genes and 238 down-regulated genes were identified. Functional and pathway enrichment analysis showed that up-regulated genes were significantly involved in cell cycle, oocyte meiosis, DNA replication and p53 signaling pathway, while down-regulated genes were enriched in Huntington's disease,metabolic pathways. Subsequently, the top 10 hub genes, (topoisomerase (DNA) II alpha), (cyclin-dependent kinase 1), (cyclin B1), (proliferating cell nuclear antigen), (mitotic arrest deficient 2 like 1), (budding uninhibited by benzimidazoles 1 homolog), (cyclin B2), (aurora kinase A), (cyclin A2), (cell division cycle 6 homolog), were identified from protein-protein interaction network. Furthermore, Module analysis revealed that the ten hub genes except were belonged to module 1, indicating the upregulation of these hub genes associated molecular pathways in nasopharyngeal carcinoma might activate nasopharyngeal carcinoma pathogenesis. In conclusion, this study indicated that the identified differentially expressed genes and hub genes enrich our understanding of the molecular mechanisms of nasopharyngeal carcinoma, which could eventually translate into additional biomarkers to facilitate the early diagnosis and therapeutic approaches.
鼻咽癌是一种起源于鼻咽上皮的转移性恶性肿瘤。早期鼻咽癌患者缺乏症状或症状不具有特异性，这显著降低了鼻咽癌诊断和预测其发展的准确性。本研究旨在识别鼻咽癌的基因特征并揭示潜在机制。对两个包含56个鼻咽癌样本和13个正常对照样本的基因表达谱（GSE12452和GSE13597）进行分析，以鉴定差异表达基因。总共鉴定出179个上调基因和238个下调基因。功能和通路富集分析表明，上调基因显著参与细胞周期、卵母细胞减数分裂、DNA复制和p53信号通路，而下调基因则富集在亨廷顿病、代谢通路中。随后，从蛋白质-蛋白质相互作用网络中鉴定出前10个枢纽基因，即拓扑异构酶（DNA）Ⅱα、细胞周期蛋白依赖性激酶1、细胞周期蛋白B1、增殖细胞核抗原、有丝分裂阻滞缺陷2样1、苯并咪唑不抑制的出芽1同源物、细胞周期蛋白B2、极光激酶A、细胞周期蛋白A2、细胞分裂周期6同源物。此外，模块分析显示，除了 外的十个枢纽基因属于模块1，这表明这些枢纽基因相关分子通路在鼻咽癌中的上调可能激活鼻咽癌的发病机制。总之，本研究表明，所鉴定的差异表达基因和枢纽基因丰富了我们对鼻咽癌分子机制的理解，最终可能转化为更多生物标志物，以促进早期诊断和治疗方法的发展。
