BDP1 Variants I1264M and V1347M Significantly Associated with Clinical Outcomes of Pediatric Neuroblastoma Patients Imply a New Prognostic Biomarker: A 121-Patient Cancer Genome Study

Li, Xiaoqing; Sun, Lan; Stucky, Andres; Tu, Langping; Cai, Jin; Chen, Xuelian; Wu, Zhongjun; Jiang, Xuhong; Li, Shengwen Calvin

doi:10.3390/diagnostics11122364

Cited by 4 publications

(9 citation statements)

References 29 publications

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“…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 ].…”

Section: Discussionmentioning

confidence: 99%

BDP1 Alterations Correlate with Clinical Outcomes in Breast Cancer

Cabarcas‐Petroski

Schramm

2022

Cancers

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TFIIIB is deregulated in a variety of cancers. However, few studies investigate the TFIIIB subunit BDP1 in cancer. BDP1 has not been studied in breast cancer patients. Herein, we analyzed clinical breast cancer datasets to determine if BDP1 alterations correlate with clinical outcomes. BDP1 copy number (n = 1602; p = 8.03 × 10−9) and mRNA expression (n = 130; p = 0.002) are specifically decreased in patients with invasive ductal carcinoma (IDC). In IDC, BDP1 copy number negatively correlates with high grade (n = 1992; p = 2.62 × 10−19) and advanced stage (n = 1992; p = 0.005). BDP1 mRNA expression also negatively correlated with high grade (n = 55; p = 6.81 × 10−4) and advanced stage (n = 593; p = 4.66 × 10−4) IDC. Decreased BDP1 expression correlated with poor clinical outcomes (n = 295 samples): a metastatic event at three years (p = 7.79 × 10−7) and cancer reoccurrence at three years (p = 4.81 × 10−7) in IDC. Decreased BDP1 mRNA correlates with patient death at three (p = 9.90 × 10−6) and five (p = 1.02 × 10−6) years. Both BDP1 copy number (n = 3785; p = 1.0 × 10−14) and mRNA expression (n = 2434; p = 5.23 × 10−6) are altered in triple-negative invasive breast cancer (TNBC). Together, these data suggest a role for BDP1 as potential biomarker in breast cancer and additional studies are warranted.

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Section: Discussionmentioning

confidence: 99%

BDP1 Alterations Correlate with Clinical Outcomes in Breast Cancer

Cabarcas‐Petroski

Schramm

2022

Cancers

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“…Recently, the BDP1 subunit of TFIIIB, has been identified as altered in human cancers. 34 , 35 , 36 Specifically, in colorectal cancer, BDP1 somatic frameshift mutations were identified, n = 98, but clinical outcome data were not reported. 37 In neuroblastoma, two BDP1 variants were identified to be associated with poor clinical outcomes 36 and recently, BDP1 expression has been correlated with clinical outcomes in non‐Hodgkin lymphoma (NHL) 35 and breast cancer.…”

Section: Introductionmentioning

confidence: 99%

“… 34 , 35 , 36 Specifically, in colorectal cancer, BDP1 somatic frameshift mutations were identified, n = 98, but clinical outcome data were not reported. 37 In neuroblastoma, two BDP1 variants were identified to be associated with poor clinical outcomes 36 and recently, BDP1 expression has been correlated with clinical outcomes in non‐Hodgkin lymphoma (NHL) 35 and breast cancer. 34 These recent BDP1 clinical cancer studies prompted our investigation of BDP1 alterations and expression in ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

BDP1 as a biomarker in serous ovarian cancer

2022

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Background: TFIIIB, an RNA polymerase III specific transcription factor has been found to be deregulated in human cancers with much of the research focused on the TBP, BRF1, and BRF2 subunits. To date, the TFIIIB specific subunit BDP1 has not been investigated in ovarian cancer but has previously been shown to be deregulated in neuroblastoma, breast cancer, and Non-Hodgkins lymphoma. Results:Using in silico analysis of clinically derived platforms, we report a decreased BDP1 expression as a result of deletion in serous ovarian cancer and a correlation with higher and advanced ovarian stages. Further analysis in the context of TP53 mutations, a major contributor to ovarian tumorigenesis, suggests that high BDP1 expression is unfavorable for overall survival and high BDP1 expression occurs in stages 2, 3 and 4 serous ovarian cancer. Additionally, high BDP1 expression is disadvantageous and unfavorable for progression-free survival. Lastly, BDP1 expression significantly decreased in patients treated with first-line chemotherapy, platin and taxane, at twelve-month relapse-free survival. Conclusions:Taken together with a ROC analysis, the data suggest BDP1 could be of clinical relevance as a predictive biomarker in serous ovarian cancer. Lastly, this study further demonstrates that both the over-and under expression of BDP1 warrants further investigation and suggests BDP1 may exhibit dual function in the context of tumorigenesis. K E Y W O R D S BDP1, ovarian cancer biomarkers, RNA polymerase III, serous ovarian cancer, TFIIIB Dataset/Description Reference Ovarian Serous Cystadenocarcinoma (TCGA, Firehose Legacy; previously known as the TCGA provisional dataset) 40 GSE26193 Transcriptome analysis of high-grade human ovarian adenocarcinomas 41 GSE63885 Gene expression profiling in ovarian cancer 42

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“…In 2021, Li et al published an article on BDP1 variants and implications in pediatric neuroblastoma patients [1]. BDP1 (B-double prime 1) was characterized as a subunit of TFIIIB required for accurate initiation by RNA polymerase III [2,3].…”

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confidence: 99%

“…The official gene symbol for brain-derived phosphatase I approved by the Hugo Gene Nomenclature Committee is PTPN18 [7]. Li et al should review the references cited demonstrating a role for BDP1 in human cancers [1]. The availability of genomics data makes it imperative for authors to strictly utilize the Hugo Gene Nomenclature Committee's approved nomenclature when analyzing available datasets and citing published research studies.…”

mentioning

confidence: 99%