Zhou Zhou, Liu Shi, Zhang Meng, Zhou Rui, Liu Jing, Chang Ying, Zhao Qiu
Department of Gastroenterology, Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei Province, People's Republic of China.
Dig Dis Sci. 2017 Oct;62(10):2790-2800. doi: 10.1007/s10620-017-4718-4. Epub 2017 Aug 16.
Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of human cancer-related death in the developed countries. Its progression and prognosis are influenced by a complex network of gene interactions.
The purpose of this study is to explore key genes associated with pancreatic ductal adenocarcinoma and to predict the possible mechanisms.
A weighted gene co-expression network was constructed to identify gene modules associated with the progression of PDAC.
In the significant module (R = 0.30), a total of 20 network hub genes were identified, 6 of which were also hub nodes in the protein-protein interaction network of the module genes. In validation, TOP2A has a higher correlation than other hub genes. Also, in the test set (n = 118), TOP2A was more highly expressed in PDAC than normal pancreas samples (P < 0.001). What is more, gene set enrichment analysis demonstrated that eight gene sets (n = 118), "nucleotide excision repair," "P53 signaling pathway," "proteasome," "mismatch repair," "homologous recombination," "DNA replication," "cell cycle," and "base excision repair," were enriched (FDR < 0.05). In gene ontology analysis, TOP2A in the enriched set was associated with cell cycle and cell division. Furthermore, survival analysis indicated that higher expression of TOP2A resulted in the lower overall survival time as well as disease-free survival time.
TOP2A was identified in association with the progression and prognosis of PDAC probably by regulating cell cycle and p53 signaling pathway.
胰腺导管腺癌（PDAC）是发达国家中人类癌症相关死亡的第四大常见原因。其进展和预后受复杂的基因相互作用网络影响。
本研究旨在探索与胰腺导管腺癌相关的关键基因，并预测可能的机制。
构建加权基因共表达网络以识别与PDAC进展相关的基因模块。
在显著模块（R = 0.30）中，共鉴定出20个网络中心基因，其中6个也是模块基因蛋白质 - 蛋白质相互作用网络中的中心节点。在验证中，TOP2A的相关性高于其他中心基因。此外，在测试集（n = 118）中，TOP2A在PDAC中的表达高于正常胰腺样本（P < 0.001）。而且，基因集富集分析表明八个基因集（n = 118），即“核苷酸切除修复”、“P53信号通路”、“蛋白酶体”、“错配修复”、“同源重组”、“DNA复制”、“细胞周期”和“碱基切除修复”被富集（FDR < 0.05）。在基因本体分析中，富集集中的TOP2A与细胞周期和细胞分裂相关。此外，生存分析表明TOP2A的高表达导致总生存时间和无病生存时间降低。
TOP2A可能通过调节细胞周期和p53信号通路与PDAC的进展和预后相关。
