Single nucleotide polymorphism and promoter methylation analysis of protein tyrosine phosphatase 1B in patients with myeloproliferative neoplasms.

IF 1.5 4区 医学 Q4 ONCOLOGY
Translational cancer research Pub Date : 2025-01-31 Epub Date: 2025-01-23 DOI:10.21037/tcr-24-1338
Jie Zhou, Hao Wu, Bing Li, Lili Zhou, Wenjun Zhang, Yi Ding, Xinyu Zhu, Huina Lu, Bing Xiu, Aibin Liang, Jianfei Fu
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引用次数: 0

Abstract

Background: The recurrent somatic mutations in genes such as Janus kinase 2 (JAK2) lead to cytokine-independent activation of the JAK-signal transducer and activator of transcription (STAT) pathway, a crucial factor in the development of classic myeloproliferative neoplasms (cMPNs). Protein tyrosine phosphatase 1B (PTP1B) is a significant regulator in this pathway, while the single nucleotide polymorphism (SNP) and promoter methylation profiles of the PTP1B gene in cMPN patients have largely remained unexplored. Therefore, to further explore the SNP and promoter methylation profiles of the PTP1B gene in cMPNs, we conducted a comprehensive SNP analysis of the PTP1B gene as well as the methylation status detection of the PTP1B promoter between cMPN patients and healthy controls.

Methods: Bone marrow (BM) biopsies were collected from a cohort comprising 96 cMPN patients and 50 healthy controls. SNP-specific extension primers were utilized to facilitate single base extension at the SNP site. A MALDI-TOF mass spectrometer and MassARRAY Typer software were used to detected the SNP. The incidence of SNPs within PTP1B were calculated in cMPN patients and healthy controls. The promoter region of the PTP1B gene were amplified and methylation Bisulfite amplicon sequencing (BSAS) analysis were performed, MethylKIT software was utilized to analyzed the methylation levels at each CpG site of PTP1B. Visualization of data was facilitated using the Methylation Plotter software. Statistical analysis of methylation was performed using the Kruskal-Wallis test. Differences of methylation at PTP1B gene sites were analyzed by Kruskal-Wallis test. P values <0.05 were considered to be statistically significant.

Results: Our findings revealed seven coding-region SNPs, including a novel variant (g.50579818T>A). Additionally, we identified aberrant hypermethylation and hypomethylation of several CpG islands within the PTP1B gene. Notably, the incidence of SNPs was significantly different between cMPN patients and healthy controls, and the methylation level of the PTP1B promoter was markedly elevated in cMPN samples compared to healthy controls.

Conclusions: In this study, we identified a novel SNP and observed differences in the frequency of seven SNPs and hypermethylation of PTP1B promoters between cMPN patients and normal controls. These results suggest that the PTP1B gene might play a critical role in the pathogenesis of cMPNs. Further research exploring more mechanism and larger sample is warranted to fully elucidate the specific role of PTP1B in cMPNs.

骨髓增殖性肿瘤患者蛋白酪氨酸磷酸酶1B的单核苷酸多态性和启动子甲基化分析。
背景:Janus kinase 2 (JAK2)等基因的反复体细胞突变可导致jak信号转导和转录激活因子(STAT)通路的细胞因子非依赖性激活,这是经典骨髓增殖性肿瘤(cmpn)发展的关键因素。蛋白酪氨酸磷酸酶1B (PTP1B)是该途径的重要调节因子,而cMPN患者PTP1B基因的单核苷酸多态性(SNP)和启动子甲基化谱在很大程度上仍未被探索。因此,为了进一步探索cMPN中PTP1B基因的SNP和启动子甲基化谱,我们对cMPN患者和健康对照进行了PTP1B基因的全面SNP分析和PTP1B启动子甲基化状态检测。方法:收集96例cMPN患者和50例健康对照者的骨髓活检。利用SNP特异性延伸引物促进SNP位点的单碱基延伸。使用MALDI-TOF质谱仪和MassARRAY Typer软件检测SNP。计算cMPN患者和健康对照中PTP1B内snp的发生率。扩增PTP1B基因启动子区,进行甲基化亚硫酸盐扩增子测序(methylation Bisulfite amplicon sequencing, BSAS)分析,利用MethylKIT软件分析PTP1B各CpG位点的甲基化水平。使用甲基化绘图仪软件方便了数据的可视化。甲基化的统计分析采用Kruskal-Wallis检验。采用Kruskal-Wallis试验分析PTP1B基因位点甲基化差异。结果:我们发现了7个编码区snp,包括一个新的变异(g.50579818T> a)。此外,我们还发现了PTP1B基因中几个CpG岛的异常高甲基化和低甲基化。值得注意的是,cMPN患者与健康对照之间snp的发生率存在显著差异,并且cMPN样本中PTP1B启动子的甲基化水平与健康对照相比显著升高。结论:在这项研究中,我们发现了一个新的SNP,并观察到cMPN患者和正常对照之间7个SNP的频率和PTP1B启动子的高甲基化的差异。这些结果提示PTP1B基因可能在cMPNs的发病机制中起关键作用。为了充分阐明PTP1B在cMPNs中的具体作用,需要进一步研究更多的机制和更大的样本。
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来源期刊
CiteScore
2.10
自引率
0.00%
发文量
252
期刊介绍: Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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