Prognostic Value Estimation of BRIP1 in Breast Cancer by Exploiting Transcriptomics Data Through Bioinformatics Approaches

Abstract

BRIP1 (Breast Cancer 1 Interacting Helicase 1) is a tumor suppressor gene that has vital function in preserving the genetic stability by repairing DNA damage though have significant associations with the onset of breast cancer (BC) if mutated or overexpressed. In this study, the prognostic value of BRIP1 gene was evaluated and validated through bioinformatics approaches utilizing transcriptomic (mRNA expression) data from several BC databases. To determine the prognostic value, the expression level of mRNA transcript was analyzed in context of comparison between breast tumor and normal tissues regarding clinical features, breast tumor subtypes, promoter methylation status, correlation level, mutation frequency, and survival of BC patients. BRIP1 expression was found to be significantly overexpressed in various BC molecular subtypes (e.g. PAM50, Sorlie’s) and clinical status (estrogen and progesterone receptor) than associated normal tissues which correlated with prognosis. Also, in promoter methylation level, its expression was observed as upregulated-hypomethylated regarding various clinicopathological features. Multiple data mining exhibited positive correlation between BRIP1 and INTS2 (Integrator Complex Subunit 2) expressions in BC. Further, mutation analysis revealed that BRIP1 gene was altered by acquiring both somatic and germline mutations. In addition, a total of 42 mutations; 24 missense, 8 fusion, 7 truncating, and 3 inframe mutations in BC patients was detected in BRIP1 protein. Moreover, higher BRIP1 expression was found to be correlated with poor disease-specific, disease metastasis-free, relapse-free, and overall survivals of BC patients. Since, overexpression of BRIP1 was identified to be associated with different clinical features, breast tumor subtypes, promoter methylation status, and survival of BC patients that may provide a risk of ensuing malignant transformation. Thus, lower expression of BRIP1 might hinder BC prognosis. We consider that this analysis will present a proof for BRIP1 gene to be a noteworthy molecular biomarker for BC prognosis.

Insights into the Oncogenic, Prognostic, and Immunological Role of BRIP1 in Pan-Cancer: A Comprehensive Data-Mining-Based Study

“…Whether it be OS, DSS, DFI, or PFI, BRIP1 remained as a high-risk factor in KIRP and PAAD. Although our results from TCGA database did not fnd a correlation between BRIP1 expression and prognosis of breast cancer patients, a study based specifcally on several breast cancer databases exhibited that higher BRIP1 expression was correlated with poor OS, DSS, DFI, and PFI [25]. Another study mining data of LUAD patients from the Genomic Data Commons (GDC) Data Portal indicated that BRIP1 might regulate fbroblast growth factor 22 and afect MAPK as well as Rap 1 signalling pathways in all tumor stages of LUAD, and a high level of BRIP1 showed boundary signifcance on OS [26], in consistence with our results.…”

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“…105 Huntington disease, Alzheimer disease, Hypoxic Ischemic Encephalopathy, Parkinson disease, and ischemic stroke have all been identified to have aberrant miR-124 expression. 106,107 Our findings revealed that decreased expression of miR-29a and hsa-miR-29b is a prevalent occurrence in many neurodegenerative disorders, including HD 85 and Alzheimer disease 108 and hsa-miR-16 is also a potential miRNA for HD. 109 Differentially expressed genes were then investigated further to understand more about the prospective interactions using minor candidate drugs that could cure HD.…”

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“…BRCA1 and BRCA2 are required for maintaining chromosomal stability to protect the genome from damage and to transcriptionally regulate some of the genes involved in DNA repair ( Yoshida and Miki, 2004 ). BRIP1 interacts with numerous proteins associated with the regulation of DNA damage responses and signal checkpoints which are vital for retaining chromosomal and genomic constancy ( Khan and Khan, 2021 ). ZBTB1 is a critical upstream regulator of translesion DNA synthesis and promotes chromatin remodelling and translesion DNA for DNA repair ( Kim et al, 2014 ; Zhang et al, 2020 ).…”