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.