Bie Liang-Yu, Li Dan, Mu Yu, Wang Sheng, Chen Bei-Bei, Lyu Hui-Fang, Han Li-Li, Nie Cai-Yun, Yang Chang-Cheng, Wang Lin, Ren Chuan-Chuan, Zhang Wei-Jie, Guo Ping, Shi Feng, Fan Qing-Xia, Wang Liu-Xing, Chen Xiao-Bing, Luo Su-Xia
Department of Oncology, Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital, Zhengzhou, Henan 450008, China.
Department of General Surgery, Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital, Zhengzhou, Henan 450008, China.
Chronic Dis Transl Med. 2018 Oct 23;5(1):44-52. doi: 10.1016/j.cdtm.2018.07.003. eCollection 2019 Mar.
To explore genes potentially co-expressed with cyclin E in gastric cancer and discover possible targets for gastric cancer treatment.
The Cancer Genome Atlas (TCGA) stomach adenocarcinoma sequencing data were used to predict genes co-expressed with cyclin E. Co-expression genes predicted by cBioPortal online analysis with Pearson correlation coefficient ≥0.4 were analyzed by gene ontology (GO) enrichment annotation using the PANTHER online platform (Ver. 7). Interactions between proteins encoded by these genes were analyzed using the STRING online platform (Ver. 10.5) and Cytoscape software (Ver. 3.5.1). Genes displaying a high degree of connection were analyzed by transcription factor enrichment prediction using FunRich software (Ver. 3). The significant transcription factor and cyclin E expression levels and their impact on gastric cancer progression were analyzed by Western blotting and Kaplan-Meier survival curve analysis.
After filtering the co-expression gene prediction results, 78 predicted genes that included 73 protein coding genes and 5 non-coding genes with Pearson correlation coefficient ≥0.4 were selected. The expressions of the genes were considered to be correlated with cyclin E expression. Among the 78 genes co-expressed with cyclin E, 19 genes at the central of the regulatory network associated with cyclin E were discovered. Nuclear transcription factor Y subunit alpha (NF-YA) was identified as a significant transcription factor associated with cyclin E co-expressing genes. Analysis of specimen donors' clinical records revealed that high expression of NF-YA tended to be associated with increased cyclin E expression. The expression of both was associated with progression of gastric cancer. Western blotting results showed that compared with normal tissues, NF-YA and cyclin E were highly expressed in tumor tissues ( < 0.001). Survival curve analysis clearly demonstrated relatively poor overall survival of gastric cancer patients with high cyclin E or high NF-YA expression level, compared to patients with low cyclin E or NF-YA expression ( < 0.05).
NF-YA may promote gastric cancer progression by increasing the transcription of cyclin E and other cell cycle regulatory genes. NF-YA might be a potential therapeutically useful prognostic factor for gastric cancer.
探索在胃癌中可能与细胞周期蛋白E共表达的基因，并发现胃癌治疗的潜在靶点。
利用癌症基因组图谱（TCGA）胃腺癌测序数据预测与细胞周期蛋白E共表达的基因。通过cBioPortal在线分析预测的共表达基因，其Pearson相关系数≥0.4，使用PANTHER在线平台（版本7）通过基因本体（GO）富集注释进行分析。利用STRING在线平台（版本10.5）和Cytoscape软件（版本3.5.1）分析这些基因编码的蛋白质之间的相互作用。使用FunRich软件（版本3）通过转录因子富集预测分析显示高度连接的基因。通过蛋白质印迹法和Kaplan-Meier生存曲线分析，分析显著的转录因子和细胞周期蛋白E的表达水平及其对胃癌进展的影响。
在筛选共表达基因预测结果后，选择了78个预测基因，其中包括73个蛋白质编码基因和5个Pearson相关系数≥0.4的非编码基因。这些基因的表达被认为与细胞周期蛋白E的表达相关。在与细胞周期蛋白E共表达的78个基因中，发现了19个位于与细胞周期蛋白E相关的调控网络中心的基因。核转录因子Y亚基α（NF-YA）被鉴定为与细胞周期蛋白E共表达基因相关的重要转录因子。对标本捐赠者临床记录的分析表明，NF-YA的高表达往往与细胞周期蛋白E表达的增加有关。两者的表达都与胃癌的进展有关。蛋白质印迹结果显示，与正常组织相比，NF-YA和细胞周期蛋白E在肿瘤组织中高表达（<0.001）。生存曲线分析清楚地表明，与细胞周期蛋白E或NF-YA低表达的患者相比，细胞周期蛋白E或NF-YA高表达的胃癌患者的总生存率相对较差（<0.05）。
NF-YA可能通过增加细胞周期蛋白E和其他细胞周期调控基因的转录来促进胃癌进展。NF-YA可能是胃癌潜在的治疗有用的预后因素。
