Department of Biotechnology, Institute of Biochemistry, Biotechnology and Bioinformatics, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.
Department of Biochemistry, Institute of Biochemistry, Biotechnology and Bioinformatics, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.
Genet Test Mol Biomarkers. 2021 Apr;25(4):263-275. doi: 10.1089/gtmb.2020.0249.
The elevated global burden of the breast invasive carcinoma (BRIC) and lack of appropriate biomarkers for its early detection and treatment requires extensive investigation to enhance understanding regarding BRIC associated molecular alterations. Ataxia telangiectasia mutated () is a multifunctional tumor suppressor gene, which participates in the DNA damage response pathway and cellular checkpoint activation. Several studies have reported the reduction of expression as a reliable biomarker of BRIC. However, its role as a clinicopathological feature-specific biomarker still needs to be explored. The present study was designed to investigate the mutational spectrum and expression variations of in BRIC patients exhibiting various clinicopathological features. Furthermore, we also performed a correlational analysis of clinicopathological feature-specific expression with its promoter methylation, status genetic alterations, copy number variation (CNVs), overall survival (OS), and effectiveness of various anticancerous drugs in BRIC patients. We utilized multiple online platforms, including UALCN, cBioportal, and CCLE GDSC tool kit. The exhibited decreased expression in the majority of the BRIC patients, and its promoter was hypermethylated compared to healthy controls. Hence, the degree of promoter methylation and expression level were inversely correlated in BRIC. In addition, we also investigated if BRIC patients that had higher expression had lower OS. We found that elevated expression of was found to promoted or decreased the effectiveness of various anticancer drugs. This study revealed the overall and clinicopathological feature-specific role of the , gene, however, these findings need to be validated via larger scale studies.
全球乳腺癌浸润性癌（BRIC）负担增加，缺乏早期检测和治疗的适当生物标志物，这需要广泛的研究来加深对 BRIC 相关分子改变的认识。共济失调毛细血管扩张突变（）是一种多功能肿瘤抑制基因，参与 DNA 损伤反应途径和细胞检查点激活。几项研究报告了表达减少作为 BRIC 的可靠生物标志物。然而，其作为临床病理特征特异性生物标志物的作用仍需要进一步探索。本研究旨在调查在表现出各种临床病理特征的 BRIC 患者中，的突变谱和表达变化。此外，我们还对临床病理特征特异性表达与其启动子甲基化、状态遗传改变、拷贝数变异（CNVs）、总生存期（OS）以及 BRIC 患者各种抗癌药物的有效性进行了相关性分析。我们利用了多个在线平台，包括 UALCN、cBioportal 和 CCLE GDSC 工具包。在大多数 BRIC 患者中，表现出表达降低，与健康对照组相比，其启动子呈超甲基化状态。因此，BRIC 中启动子甲基化程度与表达水平呈负相关。此外，我们还研究了 BRIC 患者中是否存在表达水平较高的患者 OS 较低的情况。我们发现，升高的表达水平被发现促进或降低了各种抗癌药物的有效性。这项研究揭示了的整体和临床病理特征特异性作用，然而，这些发现需要通过更大规模的研究来验证。
