Chen Yi, Wang Xuan, Wang Guan, Li Zhaozhi, Wang Jinjin, Huang Lingyu, Qin Ziyi, Yuan Xiang, Cheng Zhong, Zhang Shu, Yin Yiqiong, He Jun
Department of Gastrointestinal Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.
Mol Biosyst. 2017 May 2;13(5):991-999. doi: 10.1039/c6mb00653a.
Breast cancer has been reported as one of the most frequently diagnosed malignant diseases and the leading cause of cancer death in women all around the world. Furthermore, this complicated cancer is divided into multiple subtypes which present different clinical symptoms and need correspondingly directed therapy. We took BECN1, a core gene in autophagy performing a tumor inhibitory effect, as a starting point. The study in this paper aims to identify genes related to breast cancer and its multiple subtypes by integrating multiple omics data using the least absolute shrinkage and selection operator (LASSO), which is a statistical method that can integrate more than two types of omics data. All the data is obtained from The Cancer Genome Atlas (TCGA) platform which stores clinical and molecular tumor data. The model constructed is based on three kinds of data including mRNA-gene expression with a dependent variable level, DNA methylation and copy number alterations as independent variables. Finally, we propose four subnets of four subtypes of breast cancer, and consider as a result of microarray analysis that AFF3 is associated with BECN1 in breast cancer, and may be a potential therapeutic target. This finding may provide some potential targeted therapeutics for the four different subtypes of breast cancer at the genetic level. In conclusion, finding out the major role Beclin-1 plays in breast cancer subtypes is of great value. The results obtained are instructive for further research and may provide excellent results in clinical applications, as well as testing in animal experiments, and may also indicate a new method to perform bioinformatics analysis.
乳腺癌已被报道为全球女性中最常被诊断出的恶性疾病之一,也是癌症死亡的主要原因。此外,这种复杂的癌症可分为多种亚型,呈现出不同的临床症状,需要相应的针对性治疗。我们以自噬中的核心基因BECN1为出发点,该基因具有肿瘤抑制作用。本文的研究旨在通过使用最小绝对收缩和选择算子(LASSO)整合多组学数据来识别与乳腺癌及其多种亚型相关的基因,LASSO是一种能够整合两种以上类型组学数据的统计方法。所有数据均来自存储临床和分子肿瘤数据的癌症基因组图谱(TCGA)平台。构建的模型基于三种数据,包括以因变量水平表示的mRNA基因表达、DNA甲基化以及作为自变量的拷贝数改变。最后,我们提出了乳腺癌四种亚型的四个子网,并通过微阵列分析得出AFF3在乳腺癌中与BECN1相关,可能是一个潜在的治疗靶点。这一发现可能在基因水平上为四种不同亚型的乳腺癌提供一些潜在的靶向治疗方法。总之,弄清楚Beclin-1在乳腺癌亚型中所起的主要作用具有重要价值。所获得的结果对进一步研究具有指导意义,可能在临床应用以及动物实验测试中提供优异的结果,还可能表明一种进行生物信息学分析的新方法。