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. 2021 Dec 15;11(12):2364.
doi: 10.3390/diagnostics11122364.

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

Xiaoqing Li  1   2 , Lan Sun  1   3 , Andres Stucky  3 , Lingli Tu  3 , Jin Cai  4 , Xuelian Chen  3 , Zhongjun Wu  1   2 , Xuhong Jiang  5 , Shengwen Calvin Li  6   7
Affiliations

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

Xiaoqing Li et al. Diagnostics (Basel). .

Abstract

Background: Neuroblastoma (N.B.) is the most common tumor in children. The gene BDP1 (B Double Prime 1) plays a role in cancers but is less known in N.B. Thus, we conducted this study to investigate the value of BDP1 mutations in N.B.

Methods: A dataset of 121 NB patients from the Cancer Genome Atlas database was used to analyze BDP1 gene mutations by RNA sequencing. Kaplan-Meier estimates were performed for overall survival (O.S.) analysis on BDP1 variants, and Cox's proportional hazards regression model was used for multivariate analysis.

Results: In 121 NB patients, we identified two variants of BDP1 associated with N.B., located at chr5:71511131 and chr5:71510884. The prevalence of these BDP1 variants, I1264M and V1347M, was 52.9% (64/121) and 45.5% (55/121), respectively. O.S. analysis showed a significant difference between subgroups with or without BDP1 variants (p < 0.05). Multivariate analysis further revealed that BDP1ariants were independent prognostic variables in N.B. (p < 0.05).

Conclusion: Our results suggest BDP1 variants are associated with significantly improved clinical outcomes in N.B., thus providing clinicians with a new tool.

Keywords: BDP1; neuroblastoma; prognosis; prognostic biomarker; variant.

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Conflict of interest statement

The authors declare that they have no competing interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Association of two variants of BDP1, I1264M, and V1347M, with clinical outcomes in 121 pediatric neuroblastoma patients. Kaplan-Meier overall survival (O.S.) curves for 121 NB patients according to their BDP1 variant status. Red and green indicate variant and non-variant, respectively. Two variants of BDP1, I1264M (a) and V1347M (b), significantly improved the overall survival time. Notably, the percentage of patients without BDP1 variants was 44.6%, while 43.0% of patients harbored both (c). There was a significant difference in O.S. between them as well (d).
Figure 2
Figure 2
Role of BDP1 in the TFIIIB complex of transcription machinery in cell proliferation, cell transformation, and cancer progression. TFIIIB is a complex of the transcription machinery of RNA Pol III gene transcription [12]. TFIIIB consists of Brf1, BDP1, and TBP. Oncogenic proteins, such as c-Jun, c-Myc, Ras, and c-Fos activate TFIIIB to enhance RNA Pol III gene transcription, resulting in cancer tumorigenesis, while tumor suppressors, such as BRCA1 [13], PTEN, p53, and pRb, inactivate its activity to decrease the transcription of Pol III genes [14], leading to repression of tumor development [BDP1, a.k.a., TATA Box Binding Protein (TBP)-Associated Factor] [16]. TFIIIB). The concept of BDP1’s cancer-involved is emerging with colorectal cancers [16,17], lung cancer [18], and breast cancer [19].
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