Department of Surgery, Pusan National University Hospital, Pusan, Korea.
Cancer Epidemiol Biomarkers Prev. 2010 Feb;19(2):566-73. doi: 10.1158/1055-9965.EPI-09-0980.
This study was aimed at understanding the effects of histone modifications on recurrence-free survival (RFS) after esophagectomy in esophageal squamous cell carcinoma (ESCC). The acetylation of histone H3 lysine (H3K9Ac), histone H3 lysine 18 (H3K18Ac), and histone H4 lysine 12 (H4K12Ac), and the dimethylation of histone H3 lysine 9 (H3K9diMe) and histone H4 arginine 3 (H4R3diMe) were analyzed by immunohistochemistry in 237 ESCCs. The K-means clustering algorithm was used to identify unique patterns of histone modifications. At a median follow-up of 5.1 years, 109 (46%) of 237 patients had developed recurrence of disease. Mean global levels of H3K9Ac, H3K18Ac, H3K9diMe, H4K12Ac, and H4R3diMe were 81.5%, 65.1%, 80.3%, 45.9%, and 27.4%, respectively. In the analysis of individual histones, a 1% increase in the global level of H3K18Ac in pathologic stage III worsened RFS at 1.009 times [95% confidence interval (CI), 1.001-1.016; P = 0.03], after adjusting for age, sex, and operative method. Cluster analysis also showed significant effects of histone modifications on RFS. For stage IIB cancers, Cox proportional hazards analysis showed that RFS of cluster 1, with high global levels of H3K18Ac and H4R3diMe, was 2.79 times poorer (95% CI, 1.14-6.27; P = 0.008) than that of cluster 2, with low levels. RFS for stage III cancers was also poorer in cluster 1 than cluster 2 (adjusted hazard ratio, 2.42; 95% CI, 1.10-5.34; P = 0.02). In conclusion, the present study suggests that global levels of histone modifications in ESCC may be an independent prognostic factor of RFS.
本研究旨在探讨组蛋白修饰对食管鳞癌（ESCC）患者食管切除术后无复发生存（RFS）的影响。通过免疫组化分析了 237 例 ESCC 中组蛋白 H3 赖氨酸（H3K9Ac）、H3 赖氨酸 18（H3K18Ac）和 H4 赖氨酸 12（H4K12Ac）的乙酰化以及 H3 赖氨酸 9（H3K9diMe）和 H4 精氨酸 3（H4R3diMe）的二甲基化。采用 K-means 聚类算法识别组蛋白修饰的独特模式。在中位随访 5.1 年后，237 例患者中有 109 例（46%）发生疾病复发。H3K9Ac、H3K18Ac、H3K9diMe、H4K12Ac 和 H4R3diMe 的总体平均水平分别为 81.5%、65.1%、80.3%、45.9%和 27.4%。在单个组蛋白的分析中，病理分期 III 中 H3K18Ac 总体水平增加 1%，RFS 恶化 1.009 倍[95%置信区间（CI）：1.001-1.016；P=0.03]，校正年龄、性别和手术方法后。聚类分析还显示组蛋白修饰对 RFS 有显著影响。对于 IIB 期癌症，Cox 比例风险分析显示，具有高 H3K18Ac 和 H4R3diMe 总体水平的聚类 1 的 RFS 比聚类 2 差 2.79 倍（95%CI：1.14-6.27；P=0.008），聚类 2 的总体水平较低。III 期癌症的 RFS 在聚类 1 中也比聚类 2 差（调整后的危险比，2.42；95%CI：1.10-5.34；P=0.02）。综上所述，本研究表明 ESCC 中组蛋白修饰的总体水平可能是 RFS 的独立预后因素。
Zotero 插件