Identification of the subtypes of gastric cancer based on DNA methylation and the prediction of prognosis.
Identification of the subtypes of gastric cancer based on DNA methylation and the prediction of prognosis.
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基于DNA甲基化的胃癌亚型鉴定及预后预测
DOI：
10.1186/s13148-020-00940-3
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发表时间：
2020-10-28
影响因子：
5.7
通讯作者：
Qian C
中科院分区：
文献类型：
--
作者：
Li T;Chen X;Gu M;Deng A;Qian C
胃癌（GC）是全球死亡率很高的消化系统癌症。以往的经验和研究为临床医生提供了充分的证据，以诊断和治疗患者的合理治疗方案。然而，仍然需要敏感的生物标志物，可以为早期诊断和预后评估提供线索。在训练样本的21，121个位点中，我们发现610个独立的与凋亡相关的5′-胞嘧啶-磷酸-鸟嘌呤-3 ′（CpG）位点（P < 0.05）。我们根据所选的610个位点将GC样品分为七个聚类。聚类6具有相对较高的甲基化水平和高存活率比其他六个聚类。用第6组中显著改变的CpG位点构建预后风险模型（P < 0.05）。该模型能有效区分胃癌高危组和低危组，受试者工作特征曲线下面积为0.92。风险评估显示，高风险患者的预后比低风险患者差。在所建立的模型中，所选位点的甲基化水平随着风险评分的增加而降低。该模型已在试验组进行了验证，其有效性得到了证实。这些独立的肿瘤相关CpG的对应基因被鉴定出来，它们在多种途径中富集，例如在癌症和胃癌中的途径。其中，转化生长因子β2（transforming growth factor β2，TGFβ2）的转录水平在不同的肿瘤分期、T分期、分级及患者生存状态中存在差异，且在胃癌患者中表达较正常人明显上调。它作为癌症、肝细胞癌或胃癌的通路被包括在通路中。TGFβ2基因启动子甲基化位点为cg 11976166。这是首次使用大量样本基于CpG位点将GC分为不同分子亚型的研究。我们建立了一个有效的预后风险模型，可以识别高危胃癌患者。本研究中发现的关键CpG位点或其对应的基因如TGFβ2可以为胃肠病学家进行诊断或个性化预后评估提供新的线索，从而更好地了解这种疾病。
Gastric cancer (GC) is a digestive system cancer with a high mortality rate globally. Previous experiences and studies have provided clinicians with ample evidence to diagnose and treat patients with reasonable therapeutic options. However, there remains a need for sensitive biomarkers that can provide clues for early diagnosis and prognosis assessment. We found 610 independent prognosis-related 5′-cytosine-phosphate-guanine-3′ (CpG) sites (P < 0.05) among 21,121 sites in the training samples. We divided the GC samples into seven clusters based on the selected 610 sites. Cluster 6 had relatively higher methylation levels and high survival rates than the other six clusters. A prognostic risk model was constructed using the significantly altered CpG sites in cluster 6 (P < 0.05). This model could distinguish high-risk GC patients from low-risk groups efficiently with the area under the receiver operating characteristic curve of 0.92. Risk assessment showed that the high-risk patients had poorer prognosis than the low-risk patients. The methylation levels of the selected sites in the established model decreased as the risk scores increased. This model had been validated in testing group and its effectiveness was confirmed. Corresponding genes of the independent prognosis-associated CpGs were identified, they were enriched in several pathways such as pathways in cancer and gastric cancer. Among all of the genes, the transcript level of transforming growth factor β2 (TGFβ2) was changed in different tumor stages, T categories, grades, and patients’ survival states, and up-regulated in patients with GC compared with the normal. It was included in the pathways as pathways in cancer, hepatocellular carcinoma or gastric cancer. The methylation site located on the promoter of TGFβ2 was cg11976166. This is the first study to separate GC into different molecular subtypes based on the CpG sites using a large number of samples. We constructed an effective prognosis risk model that can identify high-risk GC patients. The key CpGs sites or their corresponding genes such as TGFβ2 identified in this research can provide new clues that will enable gastroenterologists to make diagnosis or personalized prognosis assessments and better understand this disease.
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影响因子：
2.7
作者：
Cao L;Chen Y;Zhang M;Xu DQ;Liu Y;Liu T;Liu SX;Wang P
通讯作者：
Wang P
影响因子：
3.8
作者：
Bhattacharjee, Atanu;Rajendra, Jacinth;Dutt, Shilpee
通讯作者：
Dutt, Shilpee
DOI：
10.1111/apm.1965.64.1.31
发表时间：
1965-01-01
期刊：
ACTA PATHOLOGICA ET MICROBIOLOGICA SCANDINAVICA
影响因子：
--
作者：
LAUREN, P
通讯作者：
LAUREN, P
影响因子：
4
作者：
Hu, Jing;Xu, Lutong;Chen, Qiang
通讯作者：
Chen, Qiang
影响因子：
5.2
作者：
Alabi, Nikolay;Sheka, Dropen;Wang, Edwin
通讯作者：
Wang, Edwin