BCL2 Regulation according to Molecular Subtype of Breast Cancer by Analysis of The Cancer Genome Atlas Database.
- Author:
Ki Tae HWANG
1
;
Kwangsoo KIM
;
Ji Hyun CHANG
;
Sohee OH
;
Young A KIM
;
Jong Yoon LEE
;
Se Hee JUNG
;
In Sil CHOI
Author Information
- Publication Type:Original Article
- Keywords: BCL2; Breast neoplasms; Gene expression regulation; Molecular subtype; The Cancer Genome Atlas
- MeSH: Breast Neoplasms*; Breast*; DNA; Down-Regulation; Estrogens; Gene Expression Regulation; Genome*; Humans; Lymphoma, B-Cell; Methylation; Phenobarbital; Prognosis; Protein Array Analysis; Receptor, Epidermal Growth Factor; Receptors, Progesterone; RNA; RNA, Messenger; Up-Regulation
- From:Cancer Research and Treatment 2018;50(3):658-669
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: We investigated B-cell lymphoma 2 (BCL2) regulation across DNA, RNA, protein, and methylation status according to molecular subtype of breast cancer using The Cancer Genome Atlas (TCGA) database. MATERIALS AND METHODS: We analyzed clinical and biological data on 1,096 breast cancers from the TCGA database. Biological data included reverse phase protein array (RPPA), mRNA sequencing (mRNA-seq), mRNA microarray, methylation, copy number alteration linear, copy number alteration nonlinear, and mutation data. RESULTS: The luminal A and luminal B subtypes showed upregulated expression of RPPA and mRNAseq and hypomethylation compared to the human epidermal growth factor receptor 2 (HER2) and triple-negative subtypes (all p < 0.001). No mutations were found in any subjects. High mRNA-seq and high RPPA were strongly associated with positive estrogen receptor, positive progesterone receptor (all p < 0.001), and negative HER2 (p < 0.001 and p=0.002, respectively). Correlation analysis revealed a strong positive correlation between protein and mRNA levels and a strong negative correlation between methylation and protein and mRNA levels (all p < 0.001). The high BCL2 group showed superior overall survival compared to the low BCL2 group (p=0.006). CONCLUSION: The regulation of BCL2 was mainly associated with methylation across the molecular subtypes of breast cancer, and luminal A and luminal B subtypes showed upregulated expression of BCL2 protein, mRNA, and hypomethylation. Although copy number alteration may have played a minor role, mutation status was not related to BCL2 regulation. Upregulation of BCL2 was associated with superior prognosis than downregulation of BCL2.
