In Silico-Analysis of the Multi-Omics Data Identified the Ataxia Telangiectasia Mutated Gene as a Potential Biomarker of Breast Invasive Carcinoma

被引:6
作者
Karamat, Uzma [1 ]
Ejaz, Samina [2 ]
Hameed, Yasir [1 ]
机构
[1] Islamia Univ Bahawalpur, Dept Biotechnol, Inst Biochem Biotechnol & Bioinformat, Bahawalpur, Pakistan
[2] Islamia Univ Bahawalpur, Dept Biochem, Inst Biochem Biotechnol & Bioinformat, Bahawalpur 63100, Pakistan
关键词
breast cancer; ATM; promoter methylation; overall survival (OS); ATM PROTEIN EXPRESSION; PROGNOSTIC-FACTORS; DOWN-REGULATION; CANCER PATIENTS; POOR-PROGNOSIS; TUMOR; CHEMOTHERAPY; INHIBITOR; MUTATIONS; CELLS;
D O I
10.1089/gtmb.2020.0249
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: 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 (ATM) 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 ATM expression as a reliable biomarker of BRIC. However, its role as a clinicopathological feature-specific biomarker still needs to be explored. Aim: The present study was designed to investigate the mutational spectrum and expression variations of ATM in BRIC patients exhibiting various clinicopathological features. Furthermore, we also performed a correlational analysis of clinicopathological feature-specific ATM expression with its promoter methylation, status genetic alterations, copy number variation (CNVs), overall survival (OS), and effectiveness of various anticancerous drugs in BRIC patients. Methods: We utilized multiple online platforms, including UALCN, cBioportal, and CCLE GDSC tool kit. Results: The ATM 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 ATM expression level were inversely correlated in BRIC. In addition, we also investigated if BRIC patients that had higher ATM expression had lower OS. We found that elevated expression of ATM was found to promoted or decreased the effectiveness of various anticancer drugs. Conclusion: This study revealed the overall and clinicopathological feature-specific role of the ATM, gene, however, these findings need to be validated via larger scale studies.
引用
收藏
页码:263 / 275
页数:13
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