摘要
背景:乳腺癌的患病率正以惊人的速度增长,因此需要探索最相关的诊断生物标志物。 RAD50是编码DNA损伤修复蛋白的癌症易感基因。它在乳腺癌中作为临床病理学特异性生物标志物的作用尚待探索。 目的:本研究旨在探讨具有不同临床病理特征的浸润癌患者中RAD50的表达及其启动子的甲基化水平变化。本研究进一步探讨了RAD50的突变谱及其表达与患者生存率以及治疗药物有效性的相关性。 方法:利用GeneCards平台对RAD50进行富集分析。有关RAD50表达,其启动子甲基化以及对患者生存的影响的信息可从TCGA和CPTAC数据库中检索到。但是,通过CCLE和GDSC数据集的基因组分析,得出了RAD50表达对肿瘤对多种药物反应的影响。 结果:在乳腺癌浸润癌的各个亚组中均发现了启动子高甲基化和RAD50表达升高。除绝经后的受试者外,观察到具有低/中等表达水平的受试者比显示高RAD50的患者存活更长的时间。 RAD50中错义突变的频率高于截短突变。发现大多数药物与RAD50表达呈正相关。 结论:RAD50启动子的甲基化状态与RAD50的表达水平呈负相关。 RAD50在乳腺癌患者中过表达,因此使肿瘤对许多抗癌药物具有耐药性。
关键词: RAD50,乳腺癌,CCLE药物,生存分析,突变图,MRN复合体,表达。
图形摘要
Current Cancer Drug Targets
Title:Overexpression of RAD50 is the Marker of Poor Prognosis and Drug Resistance in Breast Cancer Patients
Volume: 21 Issue: 2
关键词: RAD50,乳腺癌,CCLE药物,生存分析,突变图,MRN复合体,表达。
摘要:
Background: The prevalence of breast cancer is increasing at an alarming rate and thus demands exploration of the most relevant diagnostic biomarkers. RAD50 is a cancer susceptibility gene that encodes a DNA damage repairing protein. Its role in breast cancer as clinico-pathological specific biomarker has yet to be explored.
Objective: This study was aimed to investigate the RAD50 expression and its promoter’s methylation level variations in breast invasive carcinoma patients having different clinico-pathological features. This study further explored the mutational spectrum of RAD50 and the correlation of its expression with the survival of patients and the effectiveness of drugs used for treatment.
Methods: Enrichment analysis of RAD50 was accomplished using the platform of GeneCards. The information regarding RAD50 expression, its promoter methylation and impact on survival of patient was retrieved from TCGA and CPTAC databases. However, the effect of RAD50 expression on tumor’s response to various drugs was deduced through the analysis of CCLE and genomic of GDSC dataset.
Results: The promoter hyper-methylation and elevated expression of RAD50 was documented in various subgroups of breast invasive carcinoma. The subjects having low/medium expression levels were observed to survive longer than patients exhibiting high expression of RAD50 except for post-menopausal subjects. The frequency of missense mutations was higher in RAD50 than truncating mutations. Most of the drugs were found to have a positive correlation with RAD50 expression.
Conclusion: The status of RAD50 promoter’s methylation inversely correlates with the expression level of RAD50. While RAD50 is overexpressed in breast cancer patients and thus makes tumor resistant against many anti-cancer drugs.
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Cite this article as:
Overexpression of RAD50 is the Marker of Poor Prognosis and Drug Resistance in Breast Cancer Patients, Current Cancer Drug Targets 2021; 21 (2) . https://dx.doi.org/10.2174/1568009620666201009125507
DOI https://dx.doi.org/10.2174/1568009620666201009125507 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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