Combined Predictive Value of miR-140-5p，miR-20b-5p and miR-421 in Nasopharyngeal Carcinoma Tissues for Radiosensitivity
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摘要:
目的 探讨鼻咽癌组织中微小核糖核酸-140-5p（miR-140-5p）、微小核糖核酸-20b-5p（miR-20b-5p）、微小核糖核酸-421（miR-421）表达水平与放疗敏感性的关系，及各指标联合检测对放疗敏感性的预测价值。 方法 本研究为回顾性研究，选取2018年4月至2024年8月福建医科大学附属南平第一医院接受放疗的183例鼻咽癌患者，依据患者放疗敏感性分为敏感组（n = 120）和抵抗组（n = 63），比较两组临床资料及miR-140-5p、miR-20b-5p、miR-421水平，采用Logistic回归分析放疗敏感性的影响因素，采用ROC曲线分析miR-140-5p、miR-20b-5p、miR-421联合检测对放疗敏感性的预测价值。 结果 抵抗组T3～4期、N2～3期、M1期、临床分期Ⅲ～Ⅳ期、低分化程度患者占比及miR-20b-5p、miR-421高于敏感组，miR-140-5p、肿瘤退缩率低于敏感组（P < 0.05）；miR-140-5p、miR-20b-5p、miR-421是放疗敏感性的独立影响因素（P < 0.05）；miR-140-5p×临床分期、miR-20b-5p×临床分期、miR-421×临床分期、miR-140-5p×分化程度、miR-20b-5p×分化程度、miR-421×分化程度均具有统计学意义（P < 0.05）；miR-140-5p、miR-20b-5p、miR-421联合预测放疗敏感性的AUC值高于单一指标预测（P < 0.05）。 结论 鼻咽癌组织中miR-140-5p、miR-20b-5p、miR-421与患者放疗敏感性有关，三者联合可为临床预测患者放疗敏感性提供一定参考。 -
关键词:
- 鼻咽癌 /
- 微小核糖核酸-140-5p /
- 微小核糖核酸-20b-5p /
- 微小核糖核酸-421 /
- 放疗敏感性 /
- 联合检测
Abstract:Objective To investigate the relationship between the expression levels of microRNA-140-5p （miR-140-5p）, microRNA-20b-5p （miR-20b-5p）, and microRNA-421 （miR-421） in nasopharyngeal carcinoma tissues and the radiotherapy sensitivity, as well as the predictive value of combined detection of these indicators for radiotherapy sensitivity. Methods This retrospective study included 183 patients with nasopharyngeal carcinoma who received radiotherapy in Nanping First Hospital Affiliated to Fujian Medical University from April 2018 to August 2024. Patients were retrospectively selected and divided into a sensitive group （n = 120 ） and a resistance group （n = 63） according to the sensitivity of radiotherapy. Clinical data and levels of miR-140-5p, miR-20b-5p and miR-421 were compared between the two groups. Logistic regression analysis was used to identify the influencing factors of radiosensitivity, and ROC curve analysis was performed to evaluate the predictive value of combined detection of the three microRNAs for radiosensitivity. Results The proportion of patients in the resistant group with T3-4, N2-3, M1, clinical stage III-IV, and low differentiation of patients, as well as the levels of miR-20b-5p and miR-421 were higher than those in the sensitive group, while the miR-140-5p level and tumor regression rate were significantly lower compared to the sensitive group （P < 0.05）; miR-140-5p, miR-20b-5p, and miR-421 were independent factors affecting radiotherapy sensitivity （P < 0.05）. The interaction terms （ miR-140-5p × clinical stage, miR-20b-5p × clinical stage, miR-421 × clinical stage, miR-140-5p × differentiation degree, miR-20b-5p × differentiation degree, miR-421 × differentiation degreee） were all statistically significant （P < 0.05）. The AUC for the combined detection of miR-140-5p, miR-20b-5p, and miR-421 in predicting radiotherapy sensitivity was significantly higher than that of any single index （P < 0.05）. Conclusion The levels of miR-140-5p, miR-20b-5p, and miR-421 in nasopharyngeal carcinoma tissues are associated with the sensitivity of radiotherapy. Their combined detection can provide a clinical reference for predicting the sensitivity of radiotherapy in patients. -
图 1 miR-140-5p、miR-20b-5p、miR-421RT-PCR扫描图（$ \bar x \pm s $，n = 183）
A：miR-140-5p、miR-20b-5p、miR-421检测的PCR扩增产物琼脂糖凝胶电泳图；B：miR-140-5p、miR-20b-5p、miR-421定量分析。
Figure 1. RT-PCR scanning images of miR-140-5p，miR-20b-5p，and miR-421 （$ \bar x \pm s $，n = 183）
图 2 miR-140-5p、miR-20b-5p、miR-421对放疗敏感性的预测价值
Figure 2. Predictive value of miR-140-5p，miR-20b-5p，and miR-421 for radiotherapy sensitivity
表 1 引物序列
Table 1. Primer sequences
基因名称 上游引物序列 下游引物序列 U6 5’-GCTAGCGACGTGGCGCGCA-3’ 3’-CACGTCTGACAGTGACTACC-5’ miR-140-5p 5’-CGCAGCGAGCTCAGACGA-3’ 5’-CTGCCAGTAGTCGTAAGCCT-3’ miR-20b-5p 5’-GCCGTAGACGATGGTGTATC-3’ 5’-AGTGAGCGTATCTGCTGAGC-3’ miR-421 5’-CTCACTCACATCAACAGACATTAATT-3’ 5’-TATGGTTGTTCTGCTCTCTGTGTC-3’ 
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表 2 两组临床资料比较[n（%）/$ \bar x \pm s $]
Table 2. Comparison of clinical data between the two groups[n（%）/ $ \bar x \pm s $]
资料 抵抗组（n=63） 敏感组（n=120） t/χ2 P 年龄（岁） 54.13 ± 3.69 55.01 ± 4.27 1.386 0.167 BMI（kg/m2） 22.35 ± 1.45 21.91 ± 1.60 1.824 0.070 性别 0.199 0.656 男 33（52.38） 67（55.83） 女 30（47.62） 53（44.17） T分期（原发肿瘤） 4.648 0.031* T1～2期 20（31.75） 58（48.33） T3～4期 43（68.25） 62（51.67） N分期（区域淋巴结） 5.623 0.018* N0～1期 22（34.92） 64（53.33） N2～3期 41（65.08） 56（46.67） M分期（远处转移） 9.298 0.002* M0期 50（79.37） 113（94.63） M1期 13（20.63） 7（5.83） 临床分期 5.199 0.023* Ⅰ～Ⅱ期 24（38.10） 67（55.83） Ⅲ～Ⅳ期 39（61.90） 53（44.17） 分化程度 4.418 0.036* 中高分化 27（42.86） 71（59.17） 低分化 36（57.14） 49（40.83） 联合化疗 1.214 0.271 是 41（65.08） 68（56.67） 否 22（34.92） 52（43.33） EBV感染状态 0.172 0.678 阳性 52（82.54） 96（80.00） 阴性 11（17.46） 24（20.00） WHO病理分型 0.239 0.887 角化型鳞状细胞癌 15（23.81） 26（21.67） 非角化型癌 40（63.49） 76（63.33） 基底样鳞状细胞癌 8（12.70） 18（15.00） 放疗靶区剂量参数 GTV体积（cm3） 42.13 ± 10.06 41.87 ± 9.78 0.169 0.866 CTV体积（cm3） 128.31 ± 24.61 127.94 ± 21.95 0.104 0.917 PTV体积（cm3） 245.63 ± 40.16 242.74 ± 38.64 0.474 0.636 GTV剂量（Gy） 69.10 ± 2.18 69.28 ± 2.12 0.540 0.590 CTV剂量（Gy） 60.82 ± 1.73 60.87 ± 1.68 0.189 0.850 PTV剂量（Gy） 55.09 ± 1.66 55.18 ± 1.72 0.340 0.734 肿瘤退缩率（%） 42.19 ± 13.18 78.53 ± 12.39 18.441 <0.001* *P < 0.05。
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表 3 两组miR-140-5p、miR-20b-5p、miR-421比较（$ \bar x \pm s $）
Table 3. Comparison of miR-140-5p，miR-20b-5p，and miR-421 between the two groups（$ \bar x \pm s $）
组别 n miR-140-5p miR-20b-5p miR-421 抵抗组 63 0.48 ± 0.15 5.21 ± 1.73 1.27 ± 0.41 敏感组 120 0.67 ± 0.20 3.60 ± 1.18 0.70 ± 0.23 t 6.622 7.428 12.055 P <0.001* <0.001* <0.001* *P < 0.05。
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表 4 miR-140-5p、miR-20b-5p、miR-421与放疗敏感性的Logistic回归分析
Table 4. Logistic regression analysis of miR-140-5p，miR-20b-5p，and miR-421 with radiotherapy sensitivity
变量 β S.E. Waldχ2 OR 95%CI P 模型1 miR-140-5p −0.222 0.069 10.323 0.801 0.670-0.958 <0.001* miR-20b-5p 0.434 0.128 11.483 1.543 1.130-2.107 <0.001* miR-421 0.420 0.124 11.479 1.522 1.155-2.006 <0.001* 常量 −0.270 0.080 12.441 − − <0.001* 临床分期（以Ⅰ～Ⅱ期为参照） Ⅲ～Ⅳ期 1.880 0.389 23.368 6.556 2.146-20.031 <0.001* 分化程度（以中高分化为参照） 低分化 1.577 0.415 14.441 4.841 1.724-13.592 <0.001* miR-140-5p −0.283 0.075 14.245 0.753 0.628-0.904 <0.001* miR-20b-5p 0.539 0.136 15.685 1.714 1.203-2.441 <0.001* miR-421 0.517 0.124 17.354 1.676 1.219-2.305 <0.001* 常量 −0.437 0.108 14.063 − − <0.001* 注：*P < 0.05；模型1为只纳入miR-140-5p、miR-20b-5p、miR-421；模型2为纳入临床分期、分化程度、miR-140-5p、miR-20b-5p、miR-421。
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表 5 miR-140-5p、miR-20b-5p、miR-421对放疗敏感性的预测价值
Table 5. Predictive value of miR-140-5p，miR-20b-5p，and miR-421 for radiotherapy sensitivity
指标 AUC P 95%CI 敏感度（%） 特异度（%） 约登指数 最佳截断值 miR-140-5p 0.745 <0.001* 0.676～0.807 68.25 70.00 0.383 0.57 miR-20b-5p 0.757 <0.001* 0.688～0.817 68.25 71.67 0.399 4.19 miR-421 0.762 <0.001* 0.694～0.822 66.67 75.83 0.425 0.92 Joint 0.914 <0.001* 0.863～0.950 82.54 92.50 0.750 − *P < 0.05。
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