scholarly journals Differential methylation hybridization profiling identifies involvement of STAT1-mediated pathways in breast cancer

Author(s):  
Han-Sung Kang
2020 ◽  
Vol 16 ◽  
pp. 174480692093650 ◽  
Author(s):  
Kord M Kober ◽  
Man-Cheung Lee ◽  
Adam Olshen ◽  
Yvette P Conley ◽  
Marina Sirota ◽  
...  

Background Paclitaxel is an important chemotherapeutic agent for the treatment of breast cancer. Paclitaxel-induced peripheral neuropathy (PIPN) is a major dose-limiting toxicity that can persist into survivorship. While not all survivors develop PIPN, for those who do, it has a substantial negative impact on their functional status and quality of life. No interventions are available to treat PIPN. In our previous studies, we identified that the HIF-1 signaling pathway (H1SP) was perturbed between breast cancer survivors with and without PIPN. Preclinical studies suggest that the H1SP is involved in the development of bortezomib-induced and diabetic peripheral neuropathy, and sciatic nerve injury. The purpose of this study was to identify H1SP genes that have both differential methylation and differential gene expression between breast cancer survivors with and without PIPN. Methods A multi-staged integrated analysis was performed. In peripheral blood, methylation was assayed using microarray and gene expression was assayed using RNA-seq. Candidate genes in the H1SP having both differentially methylation and differential expression were identified between survivors who received paclitaxel and did (n = 25) and did not (n = 25) develop PIPN. Then, candidate genes were evaluated for differential methylation and differential expression in public data sets of preclinical models of PIPN and sciatic nerve injury. Results Eight candidate genes were identified as both differential methylation and differential expression in survivors. Of the eight homologs identified, one was found to be differential expression in both PIPN and “normal” mice dorsal root ganglia; three were differential methylation in sciatic nerve injury versus sham rats in both pre-frontal cortex and T-cells; and two were differential methylation in sciatic nerve injury versus sham rats in the pre-frontal cortex. Conclusions This study is the first to evaluate for methylation in cancer survivors with chronic PIPN. The findings provide evidence that the expression of H1SP genes associated with chronic PIPN in cancer survivors may be regulated by epigenetic mechanisms and suggests genes for validation as potential therapeutic targets.


2010 ◽  
Vol 203 (1) ◽  
pp. 93 ◽  
Author(s):  
Vladimir Strelnikov ◽  
Alexander Tanas ◽  
Viktoria Shkarupo ◽  
Ekaterina Kuznetsova ◽  
Nina Gorban ◽  
...  

2013 ◽  
Vol 142 (2) ◽  
pp. 365-380 ◽  
Author(s):  
Sabrina A. Bardowell ◽  
Joel Parker ◽  
Cheng Fan ◽  
Jamie Crandell ◽  
Charles M. Perou ◽  
...  

2011 ◽  
Vol 4 (1) ◽  
Author(s):  
Shuying Sun ◽  
Yi-Wen Huang ◽  
Pearlly S Yan ◽  
Tim HM Huang ◽  
Shili Lin

IEEE Access ◽  
2018 ◽  
Vol 6 ◽  
pp. 53533-53545 ◽  
Author(s):  
Abdulmajid F. Al-Juniad ◽  
Talal S. Qaid ◽  
Mohammad Yahya H. Al-Shamri ◽  
Mahdi H.A. Ahmed ◽  
Abeer A. Raweh

Author(s):  
А.И. Калинкин ◽  
В.О. Сигин ◽  
В.В. Стрельников ◽  
А.С. Танас

По результатам широкогеномного скрининга дифференциального метилирования в образцах рака молочной железы (РМЖ) нами было обнаружено аномальное деметилирование CpG-островка гена лейкотриенового рецептора LTB4R, которое может приводить к его эктопической экспрессии. В настоящей работе мы использовали данные, полученные при анализе 1083 образцов РМЖ в рамках проекта TCGA-BRCA, для определения влияния экспрессии LTB4R на эффективность лечения циклофосфамидом. Анализ кривых выживаемости пациенток с трижды-негативным (ТН) РМЖ с высокой экспрессией LTB4R в опухолях показал увеличение общей выживаемости при лечении циклофосфамидом (p<0,05). Для LumB подтипа РМЖ эффект циклофосфамида не зависел от экспрессии LTB4R. Полученные результаты расширяют возможности персонализации терапии РМЖ. Based on the results of genome-wide screening of differential methylation in breast cancer samples (BC), we have identified abnormal demethylation of the LTB4R leukotriene receptor gene CpG island, which can lead to its ectopic expression. In this paper, we used the data obtained for 1083 BC samples under the TCGA-BRCA project to determine impact of LTB4R expression on the effectiveness of treatment with cyclophosphamide. Analysis of survival curves for patients with triple-negative (TN) breast cancer and high expression of LTB4R showed an increase in overall survival of patients treated with cyclophosphamide (p <0.05). For LumB BC subtype, the effect of cyclophosphamide was not dependent on LTB4R expression. The results obtained expand the possibilities of personalizing BC therapy.


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