Cancer Res Treat.  2018 Jul;50(3):658-669. 10.4143/crt.2017.134.

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

Affiliations
  • 1Department of Surgery, SMG-SNU Boramae Medical Center, Seoul, Korea. kiterius@snu.ac.kr
  • 2Division of Clinical Bioinformatics, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
  • 3Department of Radiation Oncology, SMG-SNU Boramae Medical Center, Seoul, Korea.
  • 4Department of Biostatistics, SMG-SNU Boramae Medical Center, Seoul, Korea.
  • 5Department of Pathology, SMG-SNU Boramae Medical Center, Seoul, Korea.
  • 6Department of Radiology, SMG-SNU Boramae Medical Center, Seoul, Korea.
  • 7Department of Rehabilitation Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea.
  • 8Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea.

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.

Keyword

BCL2; Breast neoplasms; Gene expression regulation; Molecular subtype; The Cancer Genome Atlas

MeSH Terms

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
DNA
Estrogens
Phenobarbital
RNA
RNA, Messenger
Receptor, Epidermal Growth Factor
Receptors, Progesterone
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