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缺氧诱导因子-1α 与组蛋白 Lys 甲基化协同作用预测食管鳞癌预后。

Hypoxia-inducible factor-1α cooperates with histone Lys methylation to predict prognosis in esophageal squamous cell carcinoma.

机构信息

Department of Medical Genetics & Developmental Biology, Medical School of Southeast University, The Key Laboratory of Developmental Genes & Human Diseases, Ministry of Education, Southeast University, Nanjing, 210009, China.

Department of Pathology and Pathophysiology, Medical School of Southeast University, Nanjing, 210009, China.

出版信息

Biomark Med. 2021 May;15(7):509-522. doi: 10.2217/bmm-2020-0256. Epub 2021 Apr 15.

Abstract

To investigate hypoxia-inducible factor-1α (HIF-1α) and histone methylation markers as potential indicators of prognosis in esophageal squamous cell carcinoma (ESCC). The prognostic value of HIF-1α and histone methylation markers levels was analyzed using Kaplan-Meier survival analysis. HIF-1α protein expression was higher in ESCC tumors than in paracancerous tissues. Histone H3 Lys9 trimethylation (H3K9me3), histone H3 Lys27 trimethylation (H3K27me3), histone H3 Lys4 trimethylation (H3K4me3) and histone H4 Lys20 trimethylation (H4K20me3) were significantly upregulated in ESCC tissues. HIF-1α was only positively correlated with H3K9me3 and H3K4me3 expression. Kaplan-Meier analysis indicated that H3K9me3, H3K27me3, H4K20me3 and histone H3 Lys36 trimethylation (H3K36me3) were independent indicators of prognosis for ESCC. This study identified a pattern of epigenetic methylation markers and HIF-1α expression in ESCC, and their combined evaluation might improve survival prediction for ESCC patients.

摘要

为了研究缺氧诱导因子-1α(HIF-1α)和组蛋白甲基化标志物是否可作为食管鳞状细胞癌(ESCC)的预后潜在标志物。采用 Kaplan-Meier 生存分析对 HIF-1α 和组蛋白甲基化标志物水平的预后价值进行了分析。ESCC 肿瘤组织中 HIF-1α 蛋白表达高于癌旁组织。组蛋白 H3 Lys9 三甲基化(H3K9me3)、组蛋白 H3 Lys27 三甲基化(H3K27me3)、组蛋白 H3 Lys4 三甲基化(H3K4me3)和组蛋白 H4 Lys20 三甲基化(H4K20me3)在 ESCC 组织中显著上调。HIF-1α 仅与 H3K9me3 和 H3K4me3 表达呈正相关。Kaplan-Meier 分析表明,H3K9me3、H3K27me3、H4K20me3 和组蛋白 H3 Lys36 三甲基化(H3K36me3)是 ESCC 预后的独立标志物。本研究鉴定了 ESCC 中组蛋白甲基化标志物和 HIF-1α 表达的模式,它们的联合评估可能改善 ESCC 患者的生存预测。

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