Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Biosci Rep. 2019 Feb 26;39(2). doi: 10.1042/BSR20182306. Print 2019 Feb 28.
Overexpressed genes in tumors usually contributed to aggressiveness in pancreatic ductal adenocarcinoma (PDAC). Using Gene Expression Omnibus (GEO) profiles including GSE46234, GSE71989, and GSE107610, we detected overexpressed genes in tumors with R program, which were enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene ontology (GO), and Reactome pathway databases. Then, we performed a survival analysis of enriched genes based on TCGA profile. Our results revealed that high BUB1B, CCNA2, CDC20, and CDK1 expression in tumors was significantly associated with worse overall survival (OS) (Log rank =0.00338, =0.0447, =0.00965, and =0.00479, respectively), which was validated using a Kaplan-Meier plotter with a median cutoff (Log rank =0.028, =0.0035, =0.039, and =0.0033, respectively). Moreover, overexpression of BUB1B, CCNA2, CDC20, and CDK1 in tumor tissues was significantly associated with disease-free survival (DFS) in PDAC patients (Log rank =0.00565, =0.0357, =0.00104, and =0.00121, respectively). BUB1B, CCNA2, CDC20, and CDK1 were significantly overexpressed in deceased PDAC patients (all <0.01) and in patients with recurrence/disease progression (all <0.05). In addition, PDAC patients with neoplasms of histologic grade G3-4 had significantly higher BUB1B, CCNA2 and CDC20 levels (all <0.05). In conclusion, the up-regulation of BUB1B, CCNA2, CDC20, CDK1, and WEE1 in tumor tissues are associated with worse OS and DFS in PDAC and is correlated with advanced tumor stage and tumor development.
肿瘤中过表达的基因通常与胰腺导管腺癌 (PDAC) 的侵袭性有关。使用基因表达综合数据库 (GEO) 中的 GSE46234、GSE71989 和 GSE107610 进行分析，我们使用 R 程序检测到肿瘤中过表达的基因，并使用京都基因与基因组百科全书 (KEGG)、基因本体论 (GO) 和反应通路数据库进行富集。然后，我们根据 TCGA 图谱对富集基因进行生存分析。结果表明，肿瘤中 BUB1B、CCNA2、CDC20 和 CDK1 的高表达与总生存期 (OS) 较差显著相关（对数秩=0.00338，=0.0447，=0.00965 和=0.00479，分别），这一结果在 Kaplan-Meier 绘图仪中使用中位数截点得到了验证（对数秩=0.028，=0.0035，=0.039 和=0.0033，分别）。此外，BUB1B、CCNA2、CDC20 和 CDK1 在肿瘤组织中的过表达与 PDAC 患者的无病生存期 (DFS) 显著相关（对数秩=0.00565，=0.0357，=0.00104 和=0.00121，分别）。BUB1B、CCNA2、CDC20 和 CDK1 在死亡的 PDAC 患者（均<0.01）和复发/疾病进展的患者（均<0.05）中均显著过表达。此外，组织学分级 G3-4 的 PDAC 患者的 BUB1B、CCNA2 和 CDC20 水平显著升高（均<0.05）。总之，BUB1B、CCNA2、CDC20、CDK1 和 WEE1 在肿瘤组织中的上调与 PDAC 患者的 OS 和 DFS 较差相关，并且与晚期肿瘤分期和肿瘤进展相关。
