miRNA-381表达及其与鼻咽癌放疗敏感性的关系

Expression of miRNA-381 and its correlation with radiosensitivity in nasopharyngeal carcinoma

目的:观察人鼻咽癌细胞及组织中miRNA-381的表达变化,探讨其与放射敏感性的关系。方法:采用RT-PCR法测定正常鼻咽部上皮细胞株NP460,人鼻咽癌细胞株CNE-2,放疗抵抗细胞株CNE-2R及20例符合纳入标准的鼻咽癌组织中miRNA-381的表达。完成放疗后3个月接受影像学复查,分析患者的近期放疗疗效。所有病例都有2年或2年以上随访记录,根据随访记录制定放疗敏感性评估标准。采用克隆形成实验检测细胞的放疗敏感性。结果:入组患者根据放疗敏感性评估标准,分为放疗抵抗组(7例)和放疗敏感组(13例),放疗抵抗组的miRNA-381表达显著低于放疗敏感组(P<0.01)。克隆形成实验结果显示细胞的放疗敏感性为NP460>CNE-2>CNE-2R,且有显著统计学差异(P<0.01)。RT-PCR结果显示正常鼻咽部上皮细胞株NP460中miRNA-381表达量高于鼻咽癌细胞株,放疗抵抗细胞株CNE-2R中miRNA-381表达量远低于其亲代细胞株CNE-2。近期疗效和鼻咽癌组织中miRNA-381相对表达量的相关性分析显示miRNA-381相对表达量与近期疗效呈正相关(r=0.77,P<0.000 1)。结论:miRNA-381在放疗抵抗的鼻咽癌细胞及临床标本中的表达量显著低于放疗敏感的细胞及组织。miRNA-381相对表达量越高的鼻咽癌患者接受根治性放疗后的近期疗效越好。

Objective： To observe the expression of miRNA -381 in human nasopharyngeal carcinoma （NPC） ceils and tissue, and its correlation with radiosensitivity. Methods：The expression of miRNA -381 in nasopharyngeal carcinoma cell lines including the non - cancerous human immortalized nasopharyngeal epithelial cell line NP460, the human NPC cell lines CNE -2 （poorly differentiated） ,the radioresistant cell CNE -2R and nasopharyngeal carcino- ma tissue were detected by quantitative real - time PCR （ RT - PCR）. The short - term effects of patients with 3 months radical - radiotherapy in nasopharyngeal carcinoma were analyzed by imageological examination and cell radio- sensitivity was measured by colony formation assay. All cases were followed up for 2 years or more than 2 years, and radiation sensitivity evaluation criteria were based on follow - up records. Results： Nasopharyngeal carcinoma pa- tients, meeting our inclusion criteria, were divided into radioresistant group （n = 7 ） and radiosensitive group （n = 13 ） according to the radiation sensitivity evaluation criteria, miRNA - 381 was higher expressed in radiosensitive group compared with the radioresistant group （P 〈 0.01 ）. According to the radiosensitivity assay, expression of miRNA - 381 in the non - cancerous human immortalized nasopharyngeal epithelial cell NP460 was higher than that in the hu- man NPC cell lines （P 〈 0.01 ）. Moreover, the radioresistant cells CNE -2R showed lower exprssion of miRNA -381 than that of its parental cell line CNE -2 cells. Correlation analysis showed that miRNA -381 expression in nasopha- ryngeal carcinoma patients was positively correlated with the short -term effects after radical- radiotherapy （r = 0. 77 ,P 〈 0. 000 1 ）. Conclusion： Higher expression of miRNA - 381 prognosticates radiosensitivity for both patients and cell lines, and higher miRNA - 381 expression associated with better short - term effects of radical - radiotherapy treatment in nasopharyngeal carcinoma.