H3K27me3 表达对食管鳞癌放化疗后局部区域进展的预后影响。
Prognostic impact of H3K27me3 expression on locoregional progression after chemoradiotherapy in esophageal squamous cell carcinoma.
机构信息
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
出版信息
BMC Cancer. 2009 Dec 22;9:461. doi: 10.1186/1471-2407-9-461.
BACKGROUND
Trimethylation of lysine 27 on histone H3 (H3K27me3) by enhancer of zeste homolog 2 (EZH2) is an epigenetic mark that mediates gene silencing. EZH2 is overexpressed and correlates with poor prognosis in many cancers. However, the clinical implication of H3K27me3 in human malignancies has not been well established. We wished to ascertain whether a correlation exists between the expression of H3K27me3 and clinical outcome in a group of patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT).
METHODS
The method of immunohistochemistry (IHC) was utilized to examine the protein expression of H3K27me3 in 98 pretreatment biopsy specimens of ESCC and in 30 samples of normal esophageal mucosa. The clinical/prognostic significance of H3K27me3 expression was statistically analyzed.
RESULTS
The expression frequency and expression levels of H3K27me3 were significantly higher in ESCCs than in normal tissues. There was a positive correlation between H3K27me3 expression and WHO grade (P = 0.016), tumor size (P = 0.019), T status (P = 0.024), locoregional progression (P = 0.009) and EZH2 expression (P = 0.036). High H3K27me3 expression was associated with poor locoregional progression-free survival (LPFS) (P = 0.010) in ESCC. Further analysis demonstrated that H3K27me3 could stratify patient outcome in T2-3 (P = 0.048), N0 (P = 0.005) and M0 (P = 0.018) stages as well as in CRT effective group (P = 0.022).
CONCLUSIONS
Our data suggests that H3K27me3 expression examined by IHC might be useful for stratifying LPFS for different subsets of ESCC patients treated with definitive CRT.
背景
组蛋白 H3 赖氨酸 27 三甲基化（H3K27me3）由增强子结合锌指蛋白 2（EZH2）介导，是一种介导基因沉默的表观遗传标记。EZH2 在许多癌症中过度表达并与不良预后相关。然而，H3K27me3 在人类恶性肿瘤中的临床意义尚未得到很好的确立。我们希望确定在一组接受根治性放化疗（CRT）的食管鳞状细胞癌（ESCC）患者中，H3K27me3 的表达与临床结局之间是否存在相关性。
方法
采用免疫组织化学（IHC）方法检测 98 例 ESCC 患者治疗前活检标本和 30 例正常食管黏膜中 H3K27me3 的蛋白表达。对 H3K27me3 表达的临床/预后意义进行统计学分析。
结果
ESCC 中 H3K27me3 的表达频率和表达水平明显高于正常组织。H3K27me3 的表达与 WHO 分级（P = 0.016）、肿瘤大小（P = 0.019）、T 分期（P = 0.024）、局部区域进展（P = 0.009）和 EZH2 表达（P = 0.036）呈正相关。高 H3K27me3 表达与 ESCC 患者局部区域无进展生存（LPFS）不良相关（P = 0.010）。进一步分析表明，H3K27me3 可在 T2-3（P = 0.048）、N0（P = 0.005）和 M0（P = 0.018）期以及 CRT 有效组（P = 0.022）中分层患者的预后。
结论
我们的数据表明，通过 IHC 检测的 H3K27me3 表达可能有助于分层不同亚组接受根治性 CRT 的 ESCC 患者的 LPFS。
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