A meta-analysis of BRF2 as a prognostic biomarker in invasive breast carcinoma

Abstract

Background Deregulation of the RNA polymerase III specific TFIIIB subunit BRF2 occurs in subtypes of human cancers. However, correlations between BRF2 alterations and clinical outcomes in breast cancer are limited. We conducted this review to analyze BRF2 alterations in genomic data sets housed in Oncomine and cBioPortal to identify potential correlations between BRF2 alterations and clinical outcomes. Methods The authors queried both Oncomine and cBioPortal for alterations in BRF2 in human cancers and performed meta-analyses identifying significant correlations between BRF2 and clinical outcomes in invasive breast cancer (IBC). Results A meta cancer outlier profile analysis (COPA) of 715 data sets (86,733 samples) in Oncomine identified BRF2 as overexpressed in 60% of breast cancer data sets. COPA scores in IBC data sets (3594 patients) are comparable for HER2 (24.211, median gene rank 60) and BRF2 (29.656, median gene rank 36.5). Overall survival in IBC patients with BRF2 alterations (21%) is significantly decreased (p = 9.332e-3). IBC patients with BRF2 alterations aged 46 to 50 have a significantly poor survival outcome (p = 7.093e-3). Strikingly, in metastatic breast cancer, BRF2 is altered in 33% of women aged 45–50. BRF2 deletions are predominant in this age group. Conclusion This study suggests BRF2 may be an prognostic biomarker in invasive breast carcinoma.

BDP1 Alterations Correlate with Clinical Outcomes in Breast Cancer

“…The size of BDP1 has hindered researchers from working on full-length BDP1 in vitro to the extent in vitro characterization has progressed on other TFIIIB subunits. Advances in microarray and RNA-sequencing have provided a more focused approach to studying TFIIIB activity in cancer, specifically with these analyses performed using clinical samples [ 6 , 25 , 34 , 67 ].…”

“…The oncogenes MAP kinase ERK and MYC [ 11 , 17 ] stimulate TFIIIB activity in vitro. The TFIIIB subunits TBP [ 18 , 19 , 20 ], BRF1 [ 21 , 22 , 23 , 24 ], and BRF2 [ 6 , 22 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ] have begun to be studied in specific human cancers. For example, BRF2 has been classified as a novel proto-oncogene in human cancers [ 6 , 27 , 31 , 32 ].…”

ST3GAL5‐catalyzed gangliosides inhibit TGF‐β‐induced epithelial‐mesenchymal transition via TβRI degradation

“…Using a publicly available cohort of 982 lung cancer patients, we found that low expression of ST3GAL5 was associated with a poor prognosis of survival until first progression (Fig 7I ; Gyorffy et al , 2013 ). In addition, analysis of the mRNA expression level of ST3GAL5 using the Oncomine database showed that ST3GAL5 is frequently expressed at low levels in various human cancer tissues, including lung cancer tissues, compared to the corresponding adjacent normal tissues (Fig EV5F ; Neapolitan et al , 2015 ; Cabarcas‐Petroski et al , 2020 ; Saha et al , 2020 ). This finding is consistent with the results obtained by analysis of the Bhattacharjee Lung database: low levels of ST3GAL5 were detected in lung cancer compared to adjacent normal tissues (Fig 7J ; Bhattacharjee et al , 2001 ; Granville & Dennis, 2005 ).…”

Nrf2 in Cancer, Detoxifying Enzymes and Cell Death Programs

“…Recruitment of the RNA Polymerase III relies on TFIIIB, a core transcription factor composed of three subunits: (i) TBP, (ii) Bdp1 [124], and (iii) Brf2 (Brelated factor 2). Recent studies have highlighted a direct link between Brf2 over-expression and many types of cancer, including lung [125,126] and breast cancer [127,128]. The crystal structure of Brf2 in complex with TBP and the DNA revealed the presence of a conserved cysteine interacting with DNA [121].…”