BDP1 as a biomarker in serous ovarian cancer

Abstract

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

MAF1 is a predictive biomarker in HER2 positive breast cancer

“…The data used for analysis were retrieved from publicly accessible datasets. We refer readers to prior publications detailing methods [7][8][9]38].…”

“…The oncogenes MAP kinase ERK and MYC [12,18] stimulate TFIIIB activity in vitro. Specifically, the TFIIIB subunits TBP [24][25][26], BRF1 [6,[27][28][29], BRF2 [6,7,[30][31][32][33][34][35][36][37], and BDP1 [8,9,12,21,38,39] are altered in a variety of human cancers, including breast, blood, colorectal, cervical, esophageal, liver, lung, prostate, and skin cancers.…”

The importance of protein domain mutations in cancer therapy

“…However, protein domain mutations as prognostic indicators in cancer still face challenges due to the complexity of the molecular pathways of cancer growth and the potential for mutational interactions. Despite these challenges, mutation patterns can still predict disease prognosis [ 57 ]. For instance, tumors with many alterations in DNA repair genes such as BRCA1 and BRCA2 in the ovarian cancer genome can act as biomarkers in predicting the disease [ 58 ].…”