骨肉瘤细胞和组织H3K27me3表达与临床病理特征相关性研究

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目的组蛋白H3K27三甲基化(H3K27me3)在肿瘤发生发展过程中起着重要作用,研究发现H3K27me3在肝癌和前列腺癌等恶性肿瘤中的表达和临床病理特征存在相关性,但其在骨肉瘤中的研究相对较少。本研究分析H3K27me3在骨肉瘤细胞和组织中的表达及其与临床病理的关系,并探讨H3K27me3在骨肉瘤发生和发展中的作用和意义。方法所有切片均来自于河北医科大学第四医院骨科2005-01-01-2011-01-01手术切除的标本。采用蛋白印迹法检测骨肉瘤MG-63、U2-OS、Sa-OS细胞系及hFOB1.19成骨细胞中H3K27me3表达的水平差异;采用免疫组织化学染色方法检测53例骨肉瘤组织及16例骨软骨瘤组织中H3K27me3的表达水平。Kaplan-Meier分析比较H3K27me3高表达和低表达患者生存率之间的差异。并应用Cox回归模型分析其表达水平对预后影响。结果hFOB1.19、MG-63、U2-OS和Sa-OS中H3K27me3蛋白表达水平分别为0.37±0.06、0.86±0.06、0.79±0.07和0.83±0.05,与hFOB1.19细胞中H3K27me3表达相比,3组骨肉瘤细胞系中H3K27me3蛋白表达水平均显著升高,P=0.023;与骨软骨瘤组织相比(56.3%),H3K27me3在骨肉瘤组织中高表达(84.9%),二者差异有统计学意义(P<0.001),并与肿瘤大小、肺转移、Enneking分期和生存率有关,P值分别为0.037、0.020、0.023和0.046。且其表达水平与患者生存期显著相关,P=0.012。结论 H3K27me3在骨肉瘤细胞及骨肉瘤组织中呈高表达,并与肿瘤的临床病理特征相关,可能会是骨肉瘤患者重要的预后因子及治疗靶点。 The purpose of histone H3K27 trimethylation (H3K27me3) plays an important role in tumorigenesis, the study found that H3K27me3 expression in hepatocellular carcinoma and prostate cancer and other clinicopathological features are related, but in osteosarcoma The research is relatively small. This study analyzed the expression of H3K27me3 in osteosarcoma cells and tissues and its relationship with clinicopathological features and to explore the role and significance of H3K27me3 in the development and progression of osteosarcoma. Methods All the slices were from the Department of Orthopedics, the Fourth Hospital of Hebei Medical University, 2005-01-01-2011-01-01 Surgical resection specimens. Western blot was used to detect the difference of H3K27me3 expression in osteosarcoma MG-63, U2-OS, Sa-OS cell line and hFOB1.19 osteoblasts; immunohistochemistry was used to detect the expression of H3K27me3 in 53 osteosarcoma tissues and 16 cases of osteosarcoma Expression of H3K27me3 in chondroma tissues. Kaplan-Meier analysis of H3K27me3 high expression and low expression difference between the survival rate of patients. Cox regression model was used to analyze the influence of its expression on prognosis. Results The expression levels of H3K27me3 in hFOB1.19, MG-63, U2-OS and Sa-OS were 0.37 ± 0.06, 0.86 ± 0.06, 0.79 ± 0.07 and 0.83 ± 0.05, respectively. Compared with the expression of H3K27me3 in hFOB1.19 cells, Compared with osteochondroma (56.3%), the expression of H3K27me3 was significantly higher in osteosarcoma (84.9%) than that in osteochondroma (84.9%), the difference was statistically significant (P <0.001), and related to tumor size, lung metastasis, Enneking staging and survival rate, P values ​​were 0.037,0.020,0.023 and 0.046, respectively. And its expression level was significantly correlated with patient survival, P = 0.012. Conclusion H3K27me3 is overexpressed in osteosarcoma and osteosarcoma tissues and correlates with the clinicopathological features of the tumors. It may be an important prognostic factor and therapeutic target for osteosarcoma patients.
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