MAPK4 的启动子甲基化状态是胸腺瘤患者复发预后的新型表观遗传生物标志物。
Promotor methylation status of MAPK4 is a novel epigenetic biomarker for prognosis of recurrence in patients with thymic epithelial tumors.
机构信息
Department of Cancer Center, Daping Hospital, Army Medical University, Chongqing, China.
Cancer Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
出版信息
Thorac Cancer. 2022 Oct;13(20):2844-2853. doi: 10.1111/1759-7714.14628. Epub 2022 Sep 8.
BACKGROUND
The prognosis of thymic epithelial tumors (TETs) currently relies on the commonly adopted WHO classification and Masaoka staging system, which cannot reflect the undefined biological behaviors limiting them as prognostic factors.
METHODS
In this study, we first identified 40 genes and 179 genes, respectively that were epigenetically upregulated and silenced, corresponding to a total of 509 functionally methylated CpG sites between thymomas and thymic carcinomas by using the TCGA dataset.
RESULTS
The methylation β-values of cg20068620 in MAPK4 and cg18770944 in USP51 were significantly associated with recurrence-free survival (RFS). In the independent validation cohort, only WHO classification and methylation β-values of cg20068620 in MAPK4 were independent prognostic factors for RFS in Chinese patients with TETs. A linear weighted model including these two factors was used to calculate the recurrence risk score (RRS). Time-dependent ROC curve analysis revealed that RRS was overwhelmingly superior to WHO classification for predicting 3-, 5-, and 10-year RFS and Masaoka stage for 3- and 5-year RFS.
CONCLUSIONS
These results suggested that the methylation site cg20068620 in MAPK4 can improve the accuracy of the WHO classification alone regarding the prognostic value of TETs recurrence.
背景
胸腺瘤（TETs）的预后目前依赖于普遍采用的 WHO 分类和 Masaoka 分期系统，但这些系统不能反映作为预后因素的未定义的生物学行为。
方法
本研究首先通过 TCGA 数据集，分别鉴定出 40 个和 179 个在胸腺瘤和胸腺癌之间分别上调和沉默的表观遗传学基因，共对应 509 个功能甲基化 CpG 位点。
结果
MAPK4 中的 cg20068620 和 USP51 中的 cg18770944 的甲基化β值与无复发生存（RFS）显著相关。在独立验证队列中，仅 WHO 分类和 MAPK4 中的 cg20068620 的甲基化β值是中国 TETs 患者 RFS 的独立预后因素。包括这两个因素的线性加权模型用于计算复发风险评分（RRS）。时间依赖性 ROC 曲线分析表明，RRS 在预测 3、5 和 10 年 RFS 以及预测 3 和 5 年 RFS 的 Masaoka 分期方面，明显优于 WHO 分类。
结论
这些结果表明，MAPK4 中的甲基化位点 cg20068620 可单独提高 WHO 分类在 TETs 复发方面的准确性。
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