Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.
J Cell Physiol. 2019 Aug;234(8):13021-13031. doi: 10.1002/jcp.27973. Epub 2018 Dec 17.
Breast cancer (BC) is a malignant tumor which threat to women's physical and mental health. However, the mechanism of metabolism alteration in BC remains unclear. This study is intended to figure out the relationship between the alternation of metabolism and the progression of BC.
In this study, metabolites of plasma in 60 BC patients and 40 healthy volunteers were detected using liquid chromatography mass spectrometer (LC-MS). Transcriptomic data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Kyoto Encyclopedia of Genes and Genomes (KEGG) database was performed to enrich the pathways.
A total of 97 metabolites have been identified and measured, of which 17 compounds exhibited the differential expression between tumor group and control group (p < 0.05; FDR < 0.05). Metabolites set enrichment analysis (MSEA) displayed that there were 12 significantly enriched pathways in all. Through the KEGG database, 382 genes were found closely correlated with the altered metabolic pathways. TCGA and GEO transcriptomic profiling revealed that 5,018 genes significantly changed between tumor group and control group. Integrating these genes with the transcriptomic data from the corresponding KEGG data set, we identified most of the differential expressed genes were related to purine metabolism. A total of 28 different expression genes were hub genes, wherein AMPD1 and RRM2 were significantly effective in the prediction of survival of BC patients, with 0.04 and 0.02, respectively.
Combining with the transcriptomic and metabolomics data, we found that the dysregulation of purine metabolism pathway might affect the progression of BC.
乳腺癌(BC)是一种威胁女性身心健康的恶性肿瘤。然而,BC 代谢改变的机制尚不清楚。本研究旨在探讨代谢改变与 BC 进展之间的关系。
本研究采用液相色谱-质谱联用(LC-MS)检测 60 例 BC 患者和 40 例健康志愿者的血浆代谢物。从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)数据库获得转录组数据。京都基因与基因组百科全书(KEGG)数据库进行通路富集分析。
共鉴定和测量了 97 种代谢物,其中 17 种化合物在肿瘤组和对照组之间表现出差异表达(p<0.05;FDR<0.05)。代谢物集富集分析(MSEA)显示,共有 12 条通路显著富集。通过 KEGG 数据库,发现与改变的代谢途径密切相关的基因有 382 个。TCGA 和 GEO 转录组分析显示,肿瘤组和对照组之间有 5018 个基因发生显著变化。将这些基因与相应 KEGG 数据集的转录组数据整合,我们发现大多数差异表达基因与嘌呤代谢有关。共有 28 个不同表达的基因是枢纽基因,其中 AMPD1 和 RRM2 对 BC 患者的生存预测具有显著的影响,分别为 0.04 和 0.02。
结合转录组和代谢组学数据,我们发现嘌呤代谢途径的失调可能影响 BC 的进展。