BCL2 Regulation according to Molecular Subtype of Breast Cancer by Analysis of The Cancer Genome Atlas Database

• Published in: Cancer research and treatment Vol. 50; no. 3; pp. 658 - 669
• Main Authors: Hwang, Ki-Tae, Kim, Kwangsoo, Chang, Ji Hyun, Oh, Sohee, Kim, Young A, Lee, Jong Yoon, Jung, Se Hee, Choi, In Sil
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Cancer Association 01.07.2018
• Subjects: Adult; Aged; Aged, 80 and over; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Databases, Genetic; DNA Copy Number Variations; DNA Methylation; Female; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Humans; Male; Middle Aged; Neoplasm Staging; Original; Prognosis; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Survival Analysis; Up-Regulation; BCL2; Breast neoplasms; Gene expression regulation; Molecular subtype; The Cancer Genome Atlas
• DOI: 10.4143/crt.2017.134
• ISSN: 1598-2998; 2005-9256

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. 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. 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). 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.