Methylation analysis highlights novel prognostic criteria in human-metastasized melanoma
Methylation analysis highlights novel prognostic criteria in human-metastasized melanoma
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甲基化分析凸显了人类转移性黑色素瘤的新预后标准
DOI：
10.1002/jcb.28484
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发表时间：
2019-07-01
影响因子：
4
通讯作者：
Li, Zhiming
中科院分区：
文献类型：
--
作者：
Cai, Weiyang;Ding, Xiaoxia;Li, Zhiming
黑色素瘤占皮肤肿瘤相关死亡的90%，晚期患者的5年生存率约为20%。许多机制参与黑色素瘤的进展，但动态表观遗传变化可能是关键的贡献者，特别是DNA甲基化。然而，我们对黑色素瘤淋巴结转移（LNM）中涉及的甲基化事件知之甚少，这是一个特别值得关注的缺陷，因为它具有不断增长的发病率和死亡率。为了鉴定参与转移性黑色素瘤形成的DNA甲基化相关变化，我们通过Illumina Human Methylation 450 K BeadArray GSE 44661探索了原发性和LNM黑色素瘤之间的不同甲基化基因（DMG）。通过整合来自癌症基因组图谱数据库的DNA甲基化和信使RNA表达数据，我们鉴定了这些DNA甲基化生物标志物。通路分析显示这些DMG与黑色素瘤的发生密切相关，如细胞周期调控和RNA转录过程。进一步通过单因素和多因素考克斯回归分析，建立了4-DMG预后信号模型，该模型能更准确地预测黑色素瘤的预后。总之，这种基于四DMG的风险评分模型成功地预测了黑色素瘤的生存期。它独立于其他临床特征，对预后预测有一定的意义。
Melanoma accounts for 90% of the deaths associated with cutaneous neoplasms, and the 5-year survival rate of patients with the advanced stage is about 20%. Many mechanisms are involved in melanoma progression, but dynamic epigenetic changes are likely to be critical contributors, especially for DNA methylation. However, we know little about the methylation events involved in melanoma lymph node metastasis (LNM), a deficit that is of particular concern because it has a growing incidence and mortality. To identify DNA methylated-associated changes involved in the formation of metastatic melanoma, we explored the different methylated genes (DMGs) between primary and LNM melanoma by Illumina Human Methylation 450K BeadArray GSE44661. By integrating DNA methylation and messenger RNA expression data from The Cancer Genome Atlas database, we identified these DNA methylation biomarkers. Pathway analysis highlighted these DMGs, which were closely related to the carcinogenesis of melanoma, such as cell cycle regulation and RNA transcription process. Furthermore, according to the univariate and multivariate Cox regression analysis, we constructed a four-DMG prognostic signature model, which could precisely predict the outcome of melanoma in a more exact way. In summary, this four-DMG based risk score model successfully predicts the survival of melanoma. It is independent of other clinical characteristics and is good for prognosis prediction.