Zhai Xiuming, Yang Zhaowei, Liu Xiji, Dong Zihe, Zhou Dandan
Department of Laboratory Medicine, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Breast and Thyroid, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China.
PeerJ. 2020 Sep 21;8:e9975. doi: 10.7717/peerj.9975. eCollection 2020.
Breast cancer is a heterogeneous disease. Compared with other subtypes of breast cancer, triple-negative breast cancer (TNBC) is easy to metastasize and has a short survival time, less choice of treatment options. Here, we aimed to identify the potential biomarkers to TNBC diagnosis and prognosis.
MATERIAL/METHODS: Three independent data sets (GSE45827, GSE38959, GSE65194) were downloaded from the Gene Expression Omnibus (GEO). The R software packages were used to integrate the gene profiles and identify differentially expressed genes (DEGs). A variety of bioinformatics tools were used to explore the hub genes, including the DAVID database, STRING database and Cytoscape software. Reverse transcription quantitative PCR (RT-qPCR) was used to verify the hub genes in 14 pairs of TNBC paired tissues.
In this study, we screened out 161 DEGs between 222 non-TNBC and 126 TNBC samples, of which 105 genes were up-regulated and 56 were down-regulated. These DEGs were enriched for 27 GO terms and two pathways. GO analysis enriched mainly in "cell division", "chromosome, centromeric region" and "microtubule motor activity". KEGG pathway analysis enriched mostly in "Cell cycle" and "Oocyte meiosis". PPI network was constructed and then 10 top hub genes were screened. According to the analysis results of the Kaplan-Meier survival curve, the expression levels of only NUF2, FAM83D and CENPH were associated with the recurrence-free survival in TNBC samples ( < 0.05). RT-qPCR confirmed that the expression levels of NUF2 and FAM83D in TNBC tissues were indeed up-regulated significantly.
The comprehensive analysis showed that NUF2 and FAM83D could be used as potential biomarkers for diagnosis and prognosis of TNBC.
乳腺癌是一种异质性疾病。与其他乳腺癌亚型相比，三阴性乳腺癌（TNBC）易于转移，生存时间短，治疗选择较少。在此，我们旨在确定TNBC诊断和预后的潜在生物标志物。
材料/方法：从基因表达综合数据库（GEO）下载了三个独立的数据集（GSE45827、GSE38959、GSE65194）。使用R软件包整合基因谱并鉴定差异表达基因（DEG）。使用多种生物信息学工具探索枢纽基因，包括DAVID数据库、STRING数据库和Cytoscape软件。采用逆转录定量PCR（RT-qPCR）验证14对TNBC配对组织中的枢纽基因。
在本研究中，我们在222例非TNBC和126例TNBC样本之间筛选出161个DEG，其中105个基因上调，56个基因下调。这些DEG富集于27个基因本体（GO）术语和两条通路。GO分析主要富集于“细胞分裂”、“染色体，着丝粒区域”和“微管运动活性”。KEGG通路分析主要富集于“细胞周期”和“卵母细胞减数分裂”。构建蛋白质-蛋白质相互作用（PPI）网络，然后筛选出10个顶级枢纽基因。根据Kaplan-Meier生存曲线分析结果，在TNBC样本中，只有核仁蛋白2（NUF2）、家族成员83D（FAM83D）和着丝粒蛋白H（CENPH）的表达水平与无复发生存相关（P<0.05）。RT-qPCR证实TNBC组织中NUF2和FAM83D的表达水平确实显著上调。
综合分析表明，NUF2和FAM83D可作为TNBC诊断和预后的潜在生物标志物。
