Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Chengong Rd., Sec. 2, Neihu, Taipei, 114, Taiwan.
Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
BMC Cancer. 2021 Aug 21;21(1):945. doi: 10.1186/s12885-021-08645-3.
Genomic profiles of specific gene sets have been established to guide personalized treatment and prognosis for patients with breast cancer (BC). However, epigenomic information has not yet been applied in a clinical setting. ST14 encodes matriptase, a proteinase that is widely expressed in BC with reported prognostic value.
In this present study, we evaluated the effect of ST14 DNA methylation (DNAm) on overall survival (OS) of patients with BC as a representative example to promote the use of the epigenome in clinical decisions. We analyzed publicly available genomic and epigenomic data from 1361 BC patients. Methylation was characterized by the β-value from CpG probes based on sequencing with the Illumina Human 450 K platform.
A high mean DNAm (β > 0.6779) across 34 CpG probes for ST14, as the gene-associated methylation (GAM) pattern, was associated with a longer OS after adjusting age, stage, histology and molecular features in Cox model (p value < 0.001). A high GAM status was also associated with a higher XBP1 expression level and higher proportion of hormone-positive BC (p value < 0.001). Pathway analysis revealed that altered GAM was related to matrisome-associated pathway.
Here we show the potential role of ST14 DNAm in BC prognosis and warrant further study.
已经建立了特定基因集的基因组图谱，以指导乳腺癌（BC）患者的个性化治疗和预后。然而，表观基因组信息尚未在临床环境中应用。ST14 编码组织蛋白酶，一种在 BC 中广泛表达的蛋白水解酶，具有报道的预后价值。
在本研究中，我们评估了 ST14 DNA 甲基化（DNAm）对 BC 患者总生存期（OS）的影响，作为促进将表观基因组应用于临床决策的代表例子。我们分析了来自 1361 名 BC 患者的公开可用基因组和表观基因组数据。甲基化通过基于 Illumina Human 450K 平台测序的 CpG 探针的β值进行表征。
34 个 CpG 探针中 ST14 的平均 DNAm（β>0.6779）较高，作为基因相关甲基化（GAM）模式，在 Cox 模型中调整年龄、分期、组织学和分子特征后与更长的 OS 相关（p 值<0.001）。高 GAM 状态也与 XBP1 表达水平更高和激素阳性 BC 的比例更高相关（p 值<0.001）。通路分析显示，改变的 GAM 与基质体相关通路有关。
我们在这里显示了 ST14 DNAm 在 BC 预后中的潜在作用，并需要进一步研究。
