鼻咽癌组织中LncRNA CTBP1-AS2和miR-140-5p水平表达与放疗疗效及预后的关系研究

Relationship between the Expression of LncRNA CTBP1-AS2 and miR-140-5p Levels in Nasopharyngeal Carcinoma Tissues and Radiotherapeutic Effect and Prognosis

目的探讨鼻咽癌癌组织中长链非编码RNA羧基末端结合蛋白1反义RNA2(long non-coding RNA C-terminal binding protein 1 antisense RNA2,LncRNA CTBP1-AS2)、微小核糖核酸(microRNA,miR)-140-5p水平表达与放疗疗效及预后的关系。方法选取2018年3月~2020年3月于南通市肿瘤医院确诊的222例鼻咽癌患者为鼻咽癌组,记录患者临床资料,评估放疗疗效及预后,并分为生存组(n=194)和死亡组(n=28);另选取同期219例鼻咽炎患者为对照组。采用Pearson相关分析检验鼻咽癌患者中LncRNA CTBP1-AS2与miR-140-5p表达水平的相关性;采用Kaplan-Meier生存曲线分析鼻咽癌组织中LncRNA CTBP1-AS2,miR-140-5p表达水平与患者预后的关系;采用COX比例风险回归模型对鼻咽癌患者预后进行多因素分析。结果鼻咽癌组患者组织中LncRNA CTBP1-AS2表达水平(2.25±0.46)高于对照组(1.02±0.22),miR-140-5p表达水平(0.67±0.19)低于对照组(1.01±0.23),差异具有统计学意义(t=35.742,16.934,均P<0.001)。鼻咽癌患者中LncRNA CTBP1-AS2与miR-140-5p表达水平呈负相关(r=-0.624,P<0.001)。LncRNA CTBP1-AS2高表达的鼻咽癌患者放疗后总有效率(74.11%)和三年生存率(77.68%)低于低表达患者(93.64%,97.27%),差异具有统计学意义(χ^(2)=15.578,19.331,均P<0.001);miR-140-5p高表达患者放疗后总有效率(93.58%)和三年生存率(96.33%)显著高于低表达患者(74.34%,78.76%),差异具有统计学意义(χ^(2)=15.119,15.538,均P<0.001)。死亡组磁共振酰胺质子转移(amide proton transfer,APT)值(2.10±0.26)、放疗无效(85.71%)、LncRNA CTBP1-AS2高表达(89.29%)及miR-140-5p低表达(85.71%)患者比例高于生存组(1.82±0.31,6.19%,44.85%,45.88%),差异具有统计学意义(t/χ^(2)=4.551,108.127,19.331,15.538,均P<0.001)。LncRNA CTBP1-AS2表达水平为鼻咽癌患者三年内死亡的危险因素(HR=2.762,95%CI:1.510~5.051,P=0.001),miR-140-5p表达水平为鼻咽癌患者三年内死亡的保护因素(HR=0.817,95%CI:0.718~0.930,P=0.002)。结论鼻咽癌组织中LncRNA CTBP1-AS2高表达,miR-140-5p低表达,二者与放疗疗效及预后关系密切。

Objective To investigate the relationship between the expression of long non-coding RNA C-terminal binding protein 1 antisense RNA2(LncRNA CTBP1-AS2)and microRNA-140-5p(miR-140-5p)levels in nasopharyngeal carcinoma tissues and the radiotherapeutic effect and prognosis.Methods A total of 222 nasopharyngeal carcinoma patients diagnosed in Nantong Cancer Hospital from March 2018 to March 2020 were collected as the nasopharyngeal carcinoma group.The clinical data of these patients were recorded,the radiotherapeutic effect and prognosis were evaluated,and they were grouped into the survival group(n=194)and the death group(n=28).Meanwhile,another 219 patients with nasopharyngeal inflammation were collected as the control group.Correlation between LncRNA CTBP1-AS2 and miR-140-5p expression levels in nasopharyngeal carcinoma patients was calculated using Pearson correlation analysis.Kaplan-Meier survival curve was applied to analyze the relationship between the expression levels of LncRNA CTBP1-AS2 and miR-140-5p in nasopharyngeal carcinoma tissue and prognosis.Multivariate analysis was conducted on the prognosis of nasopharyngeal carcinoma patients using Cox proportional risk regression model.Results The expression level of LncRNA CTBP1-AS2 in the tissues of patients in nasopharyngeal carcinoma group(2.25±0.46)was higher than that in the control group(1.02±0.22),while the expression level of miR-140-5p(0.67±0.19)was lower than that in the control group(1.01±0.23),and the differences were statistically significant(t=35.742,16.934,all P<0.001).There was a negative correlation between LncRNA CTBP1-AS2 and miR-140-5p expression levels in nasopharyngeal carcinoma patients(r=-0.624,P<0.001).The total effective rate(74.11%)and 3-year survival rate(77.68%)of nasopharyngeal carcinoma patients with high expression of LncRNA CTBP1-AS2 after radiotherapy were lower than those with low expression(93.64%,97.27%),and the differences were statistically significant(χ^(2)=15.578,19.331,all P<0.001).The total effective rate(93.58%)and 3-year survival rate(96.33%)of patients with high expression of miR-140-5p after radiotherapy were higher than those of patients with low expression(74.34%,78.76%),and the differences were statistically significant(χ^(2)=15.119,15.538,all P<0.001).The magnetic resonance amide proton transfer(APT)value(2.10±0.26),the proportion of patients with radiotherapy failure(85.71%),high expression of LncRNA CTBP1-AS2(89.29%),and low expression of miR-140-5p(85.71%)in the death group were higher than those in the survival group(1.82±0.31,6.19%,44.85%,45.88%),and the differences were statistically significant(t/χ^(2)=4.551,108.127,19.331,15.538,all P<0.001).The level of LncRNA CTBP1-AS2 was a risk factor for mortality within 3 years in nasopharyngeal carcinoma patients(HR=2.762,95%CI:1.510~5.051,P=0.001),while the level of miR-140-5p was a protective factor for mortality within 3 years in nasopharyngeal carcinoma patients(HR=0.817,95%CI:0.718~0.930,P=0.002).Conclusion LncRNA CTBP1-AS2 was highly expressed,while miR-140-5p was lowly expressed in nasopharyngeal carcinoma tissue,indicating the two may be closely related to the radiotherapeutic effect and prognosis.