Khan Umama, Khan Md Salauddin
Biotechnology & Genetic Engineering Discipline, Khulna University, Khulna, Bangladesh.
Statistics Discipline, Khulna University, Khulna, Bangladesh.
Bioinform Biol Insights. 2021 Nov 19;15:11779322211055892. doi: 10.1177/11779322211055892. eCollection 2021.
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.
BRIP1（乳腺癌1相互作用解旋酶1）是一种肿瘤抑制基因，它通过修复DNA损伤在维持遗传稳定性方面发挥着至关重要的作用，不过如果发生突变或过表达，它与乳腺癌（BC）的发病有显著关联。在本研究中，利用来自多个BC数据库的转录组（mRNA表达）数据，通过生物信息学方法评估并验证了BRIP1基因的预后价值。为了确定预后价值，在比较乳腺肿瘤与正常组织的临床特征、乳腺肿瘤亚型、启动子甲基化状态、相关性水平、突变频率以及BC患者的生存情况的背景下，分析了mRNA转录本的表达水平。研究发现，BRIP1在各种BC分子亚型（如PAM50、Sorlie分类）和临床状态（雌激素和孕激素受体）中比相关正常组织显著过表达，这与预后相关。此外，在启动子甲基化水平方面，就各种临床病理特征而言，其表达呈现上调 - 低甲基化状态。多项数据挖掘显示，BC中BRIP1与INTS2（整合复合物亚基2）的表达呈正相关。进一步的突变分析表明，BRIP1基因通过获得体细胞和种系突变而发生改变。此外，在BRIP1蛋白中检测到BC患者共有42种突变；24种错义突变、8种融合突变、7种截短突变和3种框内突变。此外，发现较高的BRIP1表达与BC患者较差的疾病特异性、无疾病转移、无复发和总生存率相关。由于BRIP1的过表达被确定与不同的临床特征、乳腺肿瘤亚型、启动子甲基化状态以及BC患者的生存相关，这可能会带来恶性转化的风险。因此，BRIP1的低表达可能会阻碍BC的预后。我们认为，该分析将为BRIP1基因成为BC预后的一个值得关注的分子生物标志物提供证据。
