摘要
目的探讨磷酸酯酶与张力蛋白同源物(PTEN)基因甲基化在骨肉瘤发病机制、病情及预后评估中的价值。方法研究对象为2016年1月至2019年12月三亚市中医院诊治的120例骨肉瘤患者(骨肉瘤组),检测骨肉瘤患者(骨肉瘤组)和良性骨疾病患者(对照组)PTEN基因甲基化并分析与临床病理因素的关系。合成设计不同寡核苷酸(MON、UON、CON1、CON2和CON组)转染MG-63骨肉瘤细胞,对比转染前、转让后细胞PTEN基因甲基化、吸光度值、细胞增殖和凋亡的差异。两组间比较采用t或χ2检验,多组间均值比较采用SNK法分别比较组间差异。结果骨肉瘤组PTEN基因甲基化率显著高于对照组(70.8%比3.3%,χ2=12.376,P<0.05),差异有统计学意义。Saos-2、HOS和OS-732骨肉瘤细胞中PTEN呈甲基化状态,在MG-63骨肉瘤细胞为未甲基化状态。骨肉瘤组患者在Enneking分期、分化程度、肿瘤最大径和远处转移方面的PTEN基因甲基化率差异有统计学意义(χ2=4.288、3.916、5.807、7.241,P<0.05),差异均有统计学意义。MON组可成功诱导MG-63骨肉瘤细胞PTEN基因甲基化,S期、G2/M期、增殖指数和凋亡率均显著高于UON、CON1、CON2和CON组(F=51.245、43.188、71.372和90.129,P<0.05),G0/G1期显著低于UON、CON1、CON2和CON组(F=61.704,P<0.05),差异均有统计学意义。结论 PTEN基因在在骨肉瘤中呈高甲基化状态,与骨肉瘤发病机制明显相关,有助于骨肉瘤病情及预后评估。
Objective To study the effects of inactivation of phosphatase and tensin homolog deleted on chromosome 10(PTEN)gene induced by methylated oligonucleotide on biological behaviors of osteosarcoma.Methods Methylation specific polymerase chain reaction(PCR)was used to detect the PTEN gene methylation in patients with osteosarcoma and benign bone disease.The PTEN gene methylation rates in different clinicopathological factors were compared.The methylated oligonucleotide was transfected into MG-63 osteosarcoma cells.The PTEN gene methylation,absorbance,cell proliferation and apoptosis were studied before and after transfection.Results PTEN gene methylation rate in osteosarcoma group was significantly higher than in control group(70.8%vs.3.3%,χ2=12.376,P<0.05).The PTEN gene methylation rates in Enneking stage,degree of differentiation,tumor diameter and distant metastasis were significant different(χ2=4.288,3.916,5.807,7.241,P<0.05).The MON group can successfully induce the methylation of PTEN gene in MG-63 osteosarcoma cells.The S phase,G2/M phase,proliferation index and apoptosis rate were significantly higher than those of MG-63 osteosarcoma cells in the UON group,CON1 group,CON2 group,and CON group(F=51.245,43.188,71.372 and 90.129,all P<0.05),while the apoptosis rate is significantly lower than that of UON.Group,CON1 group,CON2 group and CON group(F=61.704,P<0.05).Conclusion PTEN is hypermethylated in osteosarcoma and is closely related to the disease condition and prognosis.Methylated oligonucleotides can induce inactivation of PTEN gene methylation in osteosarcoma cells,leading to increased cell proliferation and decreased apoptosis.
作者
白曼莫
王炳南
杨济
禹志军
毕方方
Bai Manmo;Wang Bingnan;Yang Ji;Yu Zhijun;Bi Fangfang(Department of Spinal Orthopedics,Sanya Hospital of TCM,Sanya 572000,China;Department of Orthopedics,the Third Affiliated Hospital of Guangzhou University of TCM,Guangzhou 510006,China;Department of Orthopedics,Wangjing Hospital of China Academy of Chinese Medical Sciences,Beijing 100102,China;Department of Neurology,Xiangya Hospital,Central South University,Changsha 410008,China)
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2020年第4期764-768,共5页
Chinese Journal of Experimental Surgery
基金
国家自然科学基金(81571256)
海南省卫生计生行业科研项目(19A200142)。
关键词
骨肉瘤
甲基化寡核苷酸
磷酸酯酶与张力蛋白同源物
Osteosarcoma
Methylated oligonucleotide
Phosphatase and tensin homolog deleted on chromosome 10
