数据挖掘分析MYB家族在乳腺癌中的表达及其预后评估价值

doi:10.3969/j.issn.1004-616x.2020.06.002

摘要/Abstract

摘要： 目的：通过数据挖掘分析MYB家族（包括MYB、MYBL1和MYBL2）在乳腺癌中的表达和预后评估价值。方法：利用Oncomine、GEPIA2、cBioPortal、bc-GenExMiner v4.4、Kaplan-Meier Plotter和DAVID数据库分析MYB家族基因在乳腺癌中的表达、变异、临床病理特征相关性、预后意义，并进行功能富集分析。结果：MYB家族在多个数据集中显示其在乳腺癌组织的表达高于正常乳腺组织（P < 0.05）。在乳腺癌中，MYB家族基因主要以基因扩增、mRNA转录增强和转录减弱的方式变异。MYB家族基因表达与乳腺癌患者年龄、分子分型、SBR分级等临床病理特征相关（P < 0.01）。其中，在三阴性乳腺癌、基底细胞样乳腺癌和P53突变型乳腺癌中，MYB低表达、MYBL1和MYBL2高表达（P < 0.01）。MYB低表达和MYBL2高表达的乳腺癌患者无复发生存期和进展后生存期缩短（P < 0.01）。单因素Cox分析结果显示，MYB低表达和MYBL2高表达的转移复发乳腺癌患者预后差（P < 0.01）。多因素Cox分析结果表明MYBL2可作为乳腺癌转移复发的独立预后因子（P < 0.05）。同时，MYBL2共表达基因主要富集于细胞分裂生物学过程和细胞周期信号通路。结论：MYB家族成员在乳腺癌转移复发过程中发挥重要作用，可作为潜在的临床诊断和预后评价标志物，为后续深入开展分子机制研究和药物开发提供了依据和方向。

关键词: MYB家族, 数据挖掘, 预后评估, 乳腺癌

Abstract: OBJECTIVE: To explore expression and prognostic values of the MYB family (MYB,MYBL1 and MYBL2) in breast cancer patients via data mining analyses. METHODS: The Oncomine database,GEPIA2,cBioPortal,bc-GenExMiner v4.4,Kaplan-Meier Plotter and DAVID were used to investigate expression distribution,genetic alteration,clinicopathological features,prognostic values and function enrichment of MYB family members in breast cancer patients. RESULTS: Expression of MYB family members were significantly higher in multiple breast cancer datasets than that in normal breast tissues (P < 0.05). Expression variation of these genes mainly involved gene amplification,and mRNA strength and weakness. Their expression levels were significantly associated with a number of clinicopathological characteristics of the patients,e.g. age,molecular subtypes,Scarff-Bloom-Richardson (SBR) grade (P < 0.01). Specifically,the mRNA expression levels of MYB were significantly downregulated,while those of MYBL1 and MYBL2 were significantly upregulated in triple negative breast cancers (TNBC),basal-like breast cancers(BLBC) and P53 mutated type breast cancers (P < 0.01).Breast cancer patients with the characteristics of low MYB and high MYBL2 mRNA expression levels showed worse relapse-free survival and post progression survival (P < 0.01). In addition,patients with metastatic recurrence of breast cancer,and low MYB and high MYBL2 expression levels had poor prognosis (Univariate Cox analyses;P < 0.01). Based on the multivariate Cox regression analyses,MYBL2 was an independent prognostic factor for metastatic recurrence survival of breast cancer patients (P < 0.05). Functional evaluation indicates that the MYBL2 co-expressed genes were mainly involved in the cell proliferation process and the cell cycle signaling pathway. CONCLUSION: Our integrative bioinformatics analyses indicate that the MYB gene family were significantly involved in metastatic relapse in breast cancer. Consequently,these genes can be used as biomarkers for clinical diagnosis and prognosis of breast cancer. Furthermore,our data provide a basis for molecular mechanism research and drug discovery for breast cancer.

Key words: MYB family, data mining, prognostic assessment, breast cancer

中图分类号:

R737.9

李玮玮, 朱莹. 数据挖掘分析MYB家族在乳腺癌中的表达及其预后评估价值[J]. 癌变·畸变·突变, 2020, 32(6): 414-422.

LI Weiwei, ZHU Ying. Data mining analyses of expression and prognostic values of the MYB family in breast cancer[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(6): 414-422.

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