Institute of Biochemistry, Biotechnology and Bioinformatics, The Islamia University of Bahawalpur, Pakistan.
Comput Biol Chem. 2021 Jun;92:107457. doi: 10.1016/j.compbiolchem.2021.107457. Epub 2021 Feb 10.
The global incidence of breast invasive carcinoma (BRIC) has risen significantly in recent years, so it is important to identify the novel biomarkers for the early detection and treatment of BRIC. The role of the TP53 gene is well studied in the pathogenesis of BRIC but still, observations are conflicting. Therefore, this study was initiated to have a consolidated overview of TP53 contributions in the BRIC initiation and progression by analyzing its mutatome, expression variations, promoter methylation level, clinical outcome, and drug sensitivity analysis in BRIC using cBioPortal, UALCAN, KM plotter, and CCLE GDSC toolkit database. Mutatome analysis revealed that TP53 was mutated in 30 % BRIC cases and among all the noted mutations, missense and truncation mutation were noticed as the most frequent mutations and thought to be involved in the up-regulation of TP53 expression. TP53 transcription, translation, and promoter methylation levels in BRIC patients of various clinicopathological features were high relative to the normal controls. Kaplan Meier overall survival (OS) analysis revealed a good prognostic value of TP53 overexpression for the survival in BRIC patients. Moreover, TP53 overexpression was found to alter the effectiveness of various drugs used in the chemotherapy of BRIC. Collectively, our findings suggested that TP53 might be a potential diagnostic and prognostic marker for the survival in BRIC patients of various clinicopathological features.
近年来,全球乳腺浸润性癌(BRIC)的发病率显著上升,因此,确定用于 BRIC 早期检测和治疗的新型生物标志物非常重要。TP53 基因在 BRIC 的发病机制中的作用已得到充分研究,但观察结果仍存在争议。因此,本研究通过分析 cBioPortal、UALCAN、KM plotter 和 CCLE GDSC 工具包数据库中的 mutatome、表达变化、启动子甲基化水平、临床结果和药物敏感性分析,旨在综合评估 TP53 在 BRIC 起始和进展中的作用。突变组分析显示,30%的 BRIC 病例中存在 TP53 突变,在所有注意到的突变中,错义突变和截断突变最为常见,被认为参与了 TP53 表达的上调。与正常对照相比,BRIC 患者的 TP53 转录、翻译和启动子甲基化水平在各种临床病理特征中均较高。Kaplan-Meier 总体生存(OS)分析显示,TP53 过表达对 BRIC 患者的生存具有良好的预后价值。此外,TP53 过表达被发现改变了 BRIC 化疗中使用的各种药物的有效性。综上所述,我们的研究结果表明,TP53 可能是预测 BRIC 患者各种临床病理特征生存的潜在诊断和预后标志物。