基于生物信息学分析MYBL2在卵巢癌耐药性中的作用及其机制

目的 研究分析MYBL2与卵巢癌耐药性之间的关系。方法 运用GEPIA在线工具分析MYBL2在正常卵巢组织与卵巢癌组织中的表达差异，运用km-plot分析卵巢癌患者关于MYBL2的总生存曲线；基于GEO Profiles数据库分析MYBL2在顺铂敏感性与顺铂耐药性的卵巢癌细胞株中的表达差异。综合运用基因互作分析、基因通路富集和文本挖掘、miRNA-mRNA相互作用分析等生物信息学方法进一步证明MYBL2调节卵巢癌耐药性及探索其内在机制。结果 卵巢癌组织中MYBL2的表达显著高于正常卵巢组织，高表达MYBL2与卵巢癌患者低生存率有关，顺铂耐药的卵巢癌细胞株MYBL2表达显著高于顺铂敏感的卵巢癌细胞株，与MYBL2具有高度关联性的基因大部分与卵巢癌耐药性有关；基因通路富集对与MYBL2相关联的基因分析发现，细胞周期富集程度最高；文本挖掘显示，除了细胞周期外，基因表达、细胞增殖、凋亡过程等生物过程与MYBL2蛋白、卵巢癌、肿瘤耐药性具有显著的关联性；miRNA-mRNA互作分析发现，靶向于MYBL2的12个miRNA皆与卵巢癌耐药性或肿瘤发生发展有关。结论 MYBL2与卵巢癌的耐药性有关，而且有可能是通过调节细胞周期而参与到卵巢癌耐药性中。

Influence of MYBL2 on Drug Resistance in Ovarian Cancer and It's Underlying Mechanism Based on Bioinformatics Analysis

OBJECTIVE To analyze the association of MYBL2 with drug resistance in ovarian cancer. METHODS Using GEPIA online tool to detect the mRNA expression of MYBL2 in normal ovary tissue and ovarian cancer. Using GEO profiles database to analyze the mRNA expression of MYBL2 in cisplatin sensitive and cisplatin resistant A2780 cell lines. Km-plot was used to perform OS survival rate. Comprehensive bioinformatic analyses were performed through protein interaction analysis, genetic pathway enrichment analysis, text mining and miRNA-mRNA interaction analysis to predict the potential pathways of MYBL2 regulated ovarian cancer drug resistance. RESULTS The expression of MYBL2 was higher in ovarian cancer compared with normal ovary. The expression of MYBL2 was higher in cisplatin resistant A2780 compared with cisplatin resistant A2780. Most proteins closely interacted with MYBL2 were associated with drug resistance in ovarian cancer. Using genetic pathway enrichment to analyze genes interacted with MYBL2, we found the most enriched pathway was cell cycle. Text mining showed besides cell cycle, gene expression, cell proliferation, apoptotic process were also significantly associated with MYBL2, ovarian cancer and drug resistance. CONCLUSION MYBL2 was associated with ovarian cancer drug resistance, and possibly by regulating cell cycle.