DNA methylation profile of inflammatory breast cancer and its impact on prognosis and outcome.

IF 4.8 2区医学 Q1 GENETICS & HEREDITY

Clinical Epigenetics Pub Date : 2024-07-06 DOI:10.1186/s13148-024-01695-x

Flavia Lima Costa Faldoni, Daniela Bizinelli, Cristiano Pádua Souza, Iara Viana Vidigal Santana, Márcia Maria Chiquitelli Marques, Claudia Aparecida Rainho, Fabio Albuquerque Marchi, Silvia Regina Rogatto

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引用次数: 0

Abstract

Background: Inflammatory breast cancer (IBC) is a rare disease characterized by rapid progression, early metastasis, and a high mortality rate.

Methods: Genome-wide DNA methylation analysis (EPIC BeadChip platform, Illumina) and somatic gene variants (105 cancer-related genes) were performed in 24 IBCs selected from a cohort of 140 cases.

Results: We identified 46,908 DMPs (differentially methylated positions) (66% hypomethylated); CpG islands were predominantly hypermethylated (39.9%). Unsupervised clustering analysis revealed three clusters of DMPs characterized by an enrichment of specific gene mutations and hormone receptor status. The comparison among DNA methylation findings and external datasets (TCGA-BRCA stages III-IV) resulted in 385 shared DMPs mapped in 333 genes (264 hypermethylated). 151 DMPs were associated with 110 genes previously detected as differentially expressed in IBC (GSE45581), and 68 DMPs were negatively correlated with gene expression. We also identified 4369 DMRs (differentially methylated regions) mapped on known genes (2392 hypomethylated). BCAT1, CXCL12, and TBX15 loci were selected and evaluated by bisulfite pyrosequencing in 31 IBC samples. BCAT1 and TBX15 had higher methylation levels in triple-negative compared to non-triple-negative, while CXCL12 had lower methylation levels in triple-negative than non-triple-negative IBC cases. TBX15 methylation level was associated with obesity.

Conclusions: Our findings revealed a heterogeneous DNA methylation profile with potentially functional DMPs and DMRs. The DNA methylation data provided valuable insights for prognostic stratification and therapy selection to improve patient outcomes.

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炎性乳腺癌的 DNA 甲基化特征及其对预后和疗效的影响

背景：炎症性乳腺癌（IBC）是一种罕见疾病，其特点是进展迅速、转移早、死亡率高：炎性乳腺癌（IBC）是一种罕见疾病，其特点是进展迅速、转移早、死亡率高：结果：我们从 140 例 IBC 中筛选出 24 例，对其进行了全基因组 DNA 甲基化分析（EPIC BeadChip 平台，Illumina）和体细胞基因变异（105 个癌症相关基因）：我们发现了 46,908 个 DMPs（差异甲基化位置）（66% 低甲基化）；CpG 岛主要是高甲基化（39.9%）。无监督聚类分析揭示了以特定基因突变和激素受体状态富集为特征的三个 DMPs 群组。通过比较DNA甲基化结果和外部数据集（TCGA-BRCA III-IV期），在333个基因中发现了385个共有的DMPs（264个高甲基化）。151 个 DMP 与之前检测到在 IBC 中差异表达的 110 个基因相关（GSE45581），68 个 DMP 与基因表达呈负相关。我们还确定了映射到已知基因上的 4369 个 DMRs（差异甲基化区域）（2392 个低甲基化）。我们在 31 个 IBC 样本中选择了 BCAT1、CXCL12 和 TBX15 位点，并通过亚硫酸氢盐热测序进行了评估。BCAT1 和 TBX15 在三阴性 IBC 中的甲基化水平高于非三阴性，而 CXCL12 在三阴性 IBC 中的甲基化水平低于非三阴性。TBX15的甲基化水平与肥胖有关：我们的研究结果揭示了一个异质性的DNA甲基化图谱，其中包含潜在的功能性DMPs和DMRs。DNA甲基化数据为预后分层和治疗选择提供了有价值的见解，从而改善了患者的预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Epigenetics ONCOLOGY-

自引率

5.30%

发文量

150

期刊介绍： Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.