晚期NSCLC放疗前后血清circPVT1和miR-486-5p水平变化及临床意义

doi:10.11958/20230346

摘要/Abstract

摘要：

目的探讨晚期非小细胞肺癌（NSCLC）患者放疗前后血清环状RNA浆细胞瘤转化迁移基因1（circPVT1）、微小RNA-486-5p（miR-486-5p）水平变化及对放疗疗效的评估价值。方法研究纳入137例晚期NSCLC患者作为NSCLC组，另选取健康体检者140例作为对照组。采用实时荧光定量PCR（qPCR）检测血清circPVT1、miR-486-5p表达水平，比较放疗前后及不同放疗疗效患者血清circPVT1和miR-486-5p水平；受试者工作特征（ROC）曲线分析血清circPVT1、miR-486-5p水平对放疗疗效的诊断价值。结果与对照组相比，NSCLC组放疗前血清circPVT1表达水平升高，miR-486-5p表达水平降低（P<0.05）；经Targetscan在线分析显示，circPVT1与miR-486-5p有靶向关系；鳞癌与腺癌NSCLC患者放疗前血清circPVT1、miR-486-5p表达水平比较差异无统计学意义（P>0.05）；与TNM分期Ⅲ期患者相比，Ⅳ期患者血清circPVT1表达水平升高，miR-486-5p表达水平降低（P<0.05）；与放疗前相比，放疗后患者血清circPVT1表达水平降低，miR-486-5p表达水平升高（P<0.05）。与放疗有效组相比，无效组放疗前和放疗后血清circPVT1表达水平升高，miR-486-5p表达水平降低（P<0.05）；与放疗前相比，放疗有效组和无效组在放疗后均显示血清circPVT1水平降低，而miR-486-5p水平升高（P<0.01）。血清circPVT1、miR-486-5p联合诊断放疗无效的AUC为0.918（95%CI：0.859~0.958），敏感度为80.65%，特异度为88.00%，联合诊断效能优于单独诊断。结论血清circPVT1、miR-486-5p水平对晚期NSCLC放疗疗效有一定评估价值。

关键词: 癌, 非小细胞肺, RNA, 环状, 化放疗, 环状RNA浆细胞瘤转化迁移基因1, 微小RNA-486-5p

Abstract:

Objective To investigate changes of serum levels of circulating RNA plasmacytoma variant translocation 1 (circPVT1) and microRNA-486-5p (miR-486-5p) before and after radiotherapy in patients with advanced non-small cell lung cancer (NSCLC) and their evaluation value for radiotherapy efficacy. Methods A total of 137 patients with advanced NSCLC were selected as the NSCLC group, and 140 health examination personnel in our hospital were selected as the control group. Real-time fluorescence quantitative PCR (RT-qPCR) was applied to detect serum expression levels of circPVT1 and miR-486-5p. Serum levels of circPVT1 and miR-486-5p before and after radiotherapy were compared. Receiver operating characteristic (ROC) curve was applied to analyze the diagnostic value of serum circPVT1 and miR-486-5p levels for radiotherapy efficacy. Results Compared with the control group, the serum expression level of circPVT1 was obviously higher before radiotherapy in the NSCLC group, and the expression level of miR-486-5p was obviously lower (P<0.05). According to Targetscan online analysis, circPVT1 had a targeted relationship with miR-486-5p. There were no significant differences in serum expression levels of circPVT1 and miR-486-5p before radiotherapy between patients with squamous cell carcinoma and adenocarcinoma NSCLC (P>0.05). Compared with TNM stage Ⅲ group, the serum expression level of circPVT1 was obviously higher in patients with stage IV NSCLC, and serum expression level of miR-486-5p was obviously lower (P<0.05). The serum expression level of circPVT1 was obviously lower in patients after radiotherapy than that before radiotherapy, and the expression level of miR-486-5p was obviously higher (P<0.05). Compared with the effective radiotherapy group, the serum expression level of circPVT1 was increased and the expression level of miR-486-5p was decreased before and after radiotherapy in the ineffective group (P<0.05). Compared with before radiotherapy, both the effective and ineffective radiotherapy groups showed a decreased serum circPVT1 level and an increased miR-486-5p level after radiotherapy (P<0.05). The AUC (95%CI: 0.859-0.958) of combined diagnosis of serum circPVT1 and miR-486-5p was 0.918, the sensitivity was 80.65% and the specificity was 88.00%. The combined diagnosis was better than single diagnosis (Z=2.06, 2.024, P<0.05). Conclusion Serum levels of circPVT1 and miR-486-5p have certain value in evaluating the efficacy of radiotherapy for advanced NSCLC.

Key words: carcinoma, non-small-cell lung, RNA, circular, chemoradiotherapy, cyclic RNA plasmacytoma variant translocation 1, micro RNA-486-5p

中图分类号:

R734.2

图/表 6

表1 对照组与NSCLC患者血清circPVT1、miR-486-5p表达水平比较（$\bar{x}\pm s$）

Tab.1 Comparison of serum circPVT1 and miR-486-5p expression levels before and after radiotherapy between the control group and the NSCLC group

组别	n		circPVT1/GAPDH
组别	n		放疗前		放疗后		t
对照组	140		1.01±0.13		-
NSCLC组	137		2.36±0.38		1.97±0.42		10.397^＊＊
t			38.472^＊＊
组别		miR-486-5p/U6
组别		放疗前		放疗后		t
对照组		1.05±0.12		-
NSCLC组		0.73±0.10		0.92±0.09		18.642^＊＊
t		24.439^＊＊

图1 circPVT1与miR-486-5p的靶向关系图

Fig.1 Targeting relationship diagram of circPVT1 and miR-486-5p

表2 NSCLC患者放疗前不同病理类型与分期血清circPVT1、miR-486-5p表达水平比较（$\bar{x}\pm s$）

Tab.2 Comparison of serum circPVT1 and miR-486-5p expression levels before radiotherapy between NSCLC patients with different pathological types and stages

临床特征	n	circPVT1	miR-486-5p
病理类型腺癌	75	2.37±0.40	0.74±0.10
鳞癌	62	2.33±0.37	0.72±0.10
t		0.697	1.200
TNM分期 Ⅲ期	81	2.23±0.31	0.76±0.08
Ⅳ期	56	2.53±0.42	0.68±0.11
t		4.525^＊＊	5.070^＊＊

表3 放疗不同疗效NSCLC患者血清circPVT1、miR-486-5p表达水平比较（$\bar{x}\pm s$）

Tab.3 Comparison of serum expression levels of circPVT1 and miR-486-5p between NSCLC patients with different therapeutic effects of radiotherapy

组别	n		circPVT1
组别	n		放疗前		放疗后		t
有效组	75		2.18±0.37		1.67±0.24		10.288^＊＊
无效组	62		2.56±0.30		2.33±0.27		4.711^＊＊
t			6.659^＊＊		15.151^＊＊
组别		miR-486-5p
组别		放疗前		放疗后		t
有效组		0.77±0.10		0.97±0.07		13.911^＊＊
无效组		0.68±0.08		0.86±0.08		12.621^＊＊
t		5.619^＊＊		9.513^＊＊

图2 放疗前血清circPVT1、miR-486-5p水平预测放疗疗效的ROC曲线

Fig.2 ROC curves of serum circPVT1 and miR-486-5p before radiotherapy

表4 放疗前血清circPVT1、miR-486-5p水平预测放疗疗效的诊断效能

Tab.4 Predicting the diagnostic efficacy of radiotherapy by serum circPVT1 and miR-486-5p levels before radiotherapy

指标	AUC	AUC 95%CI	最佳截断值	敏感度/%	特异度/%	约登指数
circPVT1	0.837	0.776~0.903	2.37	79.03	73.33	0.524
miR-486-5p	0.841	0.780~0.904	0.68	75.81	78.67	0.545
联合	0.918	0.859~0.958	-	80.65	88.00	0.687

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