Department of Medical Genetics and Developmental Biology, Medical School of Southeast University, The Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing, 210009, China.
Institute of Life Sciences, The Key Laboratory of Developmental Genes and Human Diseases, Southeast University, Nanjing, 210018, China.
Dig Dis Sci. 2019 Aug;64(8):2147-2157. doi: 10.1007/s10620-019-05529-2. Epub 2019 Feb 20.
Histone methylation, as an essential pattern of posttranslational modifications, contributes to multiple cancer-related biological processes. Dysregulation of histone methylation is now considered a biomarker for cancer prognosis.
This study investigated and evaluated the potential role of four histone lysine trimethylation markers as biomarkers for esophageal squamous cell carcinoma (ESCC) prognosis.
Tissue arrays were made from 135 paraffin-embedded ESCC samples and examined for histone markers by immunohistochemistry, and 10 pairs of cancer and noncancerous mucosa tissues from ESCC patients were investigated with Western blot. Chi-squared test, Kaplan-Meier analysis with log-rank test, and Cox proportional hazard trend analyses were performed to assess the prognostic values of the markers.
Histone 3 lysine 4 trimethylation (H3K4me3), histone 3 lysine 9 trimethylation (H3K9me3), and histone 4 lysine 20 trimethylation (H4K20me3), but not histone 3 lysine 36 trimethylation (H3K36me3), showed stronger immunostaining signals in tumor tissues than in the corresponding adjacent non-neoplastic mucosa tissues. The expression patterns of H3K36me3, H3K9me3, and H4K20me3 correlated with tumor infiltrating depth, lymph node involvement, and pTNM stage. Low-scoring H3K9me3 and H4K20me3 predicted better prognosis, while H3K36me3 manifested the opposite trend. Poor prognosis occurred in ESCC patients with expression patterns of high levels of H3K9me3, high levels of H4K20me3, and low levels of H3K36me3 expression.
H3K9me3, H4K20me3, and H3K36me3 showed a close relationship with clinical features and were considered independent risk factors for survival of ESCC patients. The combination of H3K9me3, H4K20me3, and H3K36me3 expression, rather than the expression of a single histone marker, is believed to further enhance evaluations of ESCC prognosis and management.
组蛋白甲基化作为一种重要的翻译后修饰模式，有助于多种与癌症相关的生物学过程。组蛋白甲基化失调现在被认为是癌症预后的生物标志物。
本研究探讨并评估了四种组蛋白赖氨酸三甲基化标志物作为食管鳞状细胞癌（ESCC）预后标志物的潜在作用。
制作了 135 例石蜡包埋 ESCC 样本的组织阵列，并通过免疫组织化学检查组蛋白标志物，对 10 对 ESCC 患者的癌组织和非癌组织进行 Western blot 检测。采用卡方检验、Kaplan-Meier 分析和对数秩检验以及 Cox 比例风险趋势分析评估标志物的预后价值。
组蛋白 3 赖氨酸 4 三甲基化（H3K4me3）、组蛋白 3 赖氨酸 9 三甲基化（H3K9me3）和组蛋白 4 赖氨酸 20 三甲基化（H4K20me3），但不是组蛋白 3 赖氨酸 36 三甲基化（H3K36me3），在肿瘤组织中的免疫染色信号强于相应的相邻非肿瘤黏膜组织。H3K36me3、H3K9me3 和 H4K20me3 的表达模式与肿瘤浸润深度、淋巴结受累和 pTNM 分期相关。低评分的 H3K9me3 和 H4K20me3 预测预后较好，而 H3K36me3 则表现出相反的趋势。H3K9me3 水平高、H4K20me3 水平高、H3K36me3 水平低的 ESCC 患者预后不良。
H3K9me3、H4K20me3 和 H3K36me3 与临床特征密切相关，被认为是 ESCC 患者生存的独立危险因素。H3K9me3、H4K20me3 和 H3K36me3 表达的组合，而不是单个组蛋白标志物的表达，可能进一步增强对 ESCC 预后和管理的评估。
