晚期非小细胞肺癌患者血清miR-499、miR-362水平变化及与预后的关系分析

国际肿瘤学杂志››2024,Vol. 51››Issue (8): 487-492.doi:10.3760/cma.j.cn371439-20240318-00081

晚期非小细胞肺癌患者血清miR-499、miR-362水平变化及与预后的关系分析

倪国英, 黄骞, 梁洪享, 杨志勇, 丁颖丽()

上海健康医学院附属崇明医院肿瘤科，上海 202150

收稿日期:2024-03-18修回日期:2024-06-25出版日期:2024-08-08发布日期:2024-09-24
通讯作者:丁颖丽，Email：386937117@qq.com
基金资助:
上海市崇明区“可持续发展科技创新行动计划”(CKY2020-19);上海市崇明区“可持续发展科技创新行动计划”(CKY2021-06);上海健康医学院附属崇明医院科研基金(CMYY2023-09)

Analysis of changes in serum miR-499 and miR-362 levels and their relationship with prognosis in advanced NSCLC patients

Ni Guoying, Huang Qian, Liang Hongxiang, Yang Zhiyong, Ding Yingli()

Department of Oncology，Shanghai University of Medicine & Health Sciences Affiliated Chongming Hospital，Shanghai 202150，China

Received:2024-03-18Revised:2024-06-25Online:2024-08-08Published:2024-09-24
Contact:Ding Yingli，Email：386937117@qq.com
Supported by:
The "Sustainable Development Technology Innovation Action Plan" Project in Chongming District，Shanghai(CKY2020-19);The "Sustainable Development Technology Innovation Action Plan" Project in Chongming District，Shanghai(CKY2021-06);Research Fund of Shanghai University of Medicine & Health Sciences Affitiated Chongming Hospital(CMYY2023-09)

摘要/Abstract

摘要：

目的探讨晚期非小细胞肺癌（NSCLC）患者血清miR-499、miR-362水平变化及与预后的关系。方法选取2020年1月—2021年10月上海健康医学院附属崇明医院收治的103例晚期NSCLC患者为NSCLC组，选取同期在本院体检健康的志愿者100例作为对照组。采用荧光定量PCR测定并比较两组血清miR-499、miR-362水平，并分析二者与NSCLC患者不同临床特征的关系；按照患者随访2年的临床结局将其分为生存组及死亡组，比较两组血清miR-499、miR-362水平；采用受试者操作特征（ROC）曲线分析miR-499、miR-362水平对晚期NSCLC患者预后的预测价值。结果NSCLC组血清miR-499水平（0.34±0.10）低于对照组（1.25±0.21），miR-362水平（1.13±0.27）高于对照组（0.63±0.15）（t=18.26，P<0.001；t=16.32，P<0.001）。不同分化程度（t=11.12，P<0.001；t=16.35，P<0.001）、TNM分期（t=13.64，P=0.002；t=8.73，P=0.010）、淋巴结转移情况（t=10.02，P=0.003；t=9.65，P=0.004）患者的血清miR-499、miR-362水平差异均有统计学意义。死亡组（n=77）血清miR-499水平（0.24±0.06）低于生存组（n=26）（0.35±0.09），miR-362水平（1.54±0.32）高于生存组（1.08±0.21），差异均具有统计学意义（t=8.06，P=0.006；t=8.67，P=0.005）。ROC曲线分析显示，miR-499、miR-362预测晚期NSCLC患者预后的敏感性分别为73.46%、75.85%，特异性分别为64.42%、65.61%，AUC分别为0.739（95%CI为0.662~0.805）、0.743（95%CI为0.640~0.793）；血清miR-499联合miR-362对晚期NSCLC患者预后预测价值的敏感性为87.63%，特异性为85.34%，AUC为0.875（95%CI为0.698~0.897）；miR-499、miR-362联合预测AUC面积高于单独预测（Z=4.83，P=0.013；Z=5.17，P=0.009）。结论晚期NSCLC患者血清miR-499、miR-362水平均出现明显异常，且随着病情严重程度的进展，miR-499下调更明显、miR-362上调更明显。miR-499、miR-362水平联合检测对晚期NSCLC患者预后具有一定的预测价值。

关键词:癌,非小细胞肺,miR-499,miR-362,预后

Abstract:

ObjectiveTo explore the changes in serum levels of miR-499 and miR-362 in patients with advanced non-small cell lung cancer （NSCLC） and their relationship with prognosis.MethodsA total of 103 patients with advanced NSCLC at Shanghai University of Medicine & Health Sciences Affiliated Chongming Hospital from January 2020 to October 2021 were selected as the NSCLC group，and 100 healthy volunteers who underwent physical examinations at our hospital during the same period were selected as the control group. Fluorescent quantitative PCR was used to determine and compare the levels of serum miR-499 and miR-362 in the two groups，and the relationship between the two indexes and different clinical characteristics of NSCLC patients was analyzed. According to the clinical outcome of 2-year follow-up，the patients were divided into survival group and death group，and the levels of serum miR-499 and miR-362 were compared between the two groups. The predictive value of miR-499 and miR-362 levels on the prognosis of advanced NSCLC patients were analyzed using receiver operator characteristic （ROC） curves.ResultsThe serum miR-499 level in the NSCLC group （0.34±0.10） was lower than that in the control group （1.25±0.21），while the miR-362 level （1.13±0.27） was higher than that in the control group （0.63±0.15）（t=18.26，P<0.001；t=16.32，P<0.001）. There were statistically significant differences in serum miR-499 and miR-362 levels among patients with different degrees of differentiation （t=11.12，P<0.001；t=16.35，P<0.001），TNM staging （t=13.64，P=0.002；t=8.73，P=0.010） and lymph node metastasis （t=10.02，P=0.003；t=9.65，P=0.004）. The serum miR-499 level in the death group （n=77）（0.24±0.06） was lower than that in the survival group （n=26）（0.35±0.09），while the miR-362 level （1.54±0.32） was higher than that in the survival group （1.08±0.21），with statistically significant differences （t=8.06，P=0.006；t=8.67，P=0.005）. ROC curve analysis showed that the sensitivity of miR-499 and miR-362 in predicting the prognosis of advanced NSCLC patients was 73.46% and 75.85%，respectively，with specificity of 64.42% and 65.61%，AUC of 0.739 （95%CI：0.662-0.805） and 0.743 （95%CI：0.640-0.793）； the sensitivity，specificity，and AUC of serum miR-499 combined with miR-362 in predicting the prognosis of advanced NSCLC patients were 87.63%，85.34%，and 0.875 （95%CI：0.698-0.897），respectively； the combined prediction of miR-499 and miR-362 for AUC area was higher than the individual prediction （Z=4.83，P=0.013；Z=5.17，P=0.009）.ConclusionAdvanced NSCLC patients show significant abnormal serum level of miR-499 and miR-362，and as the severity of the disease progressed，the serum level of miR-499 is downregulated more significantly and miR-362 is upregulated more significantly. The combined detection of miR-499 and miR-362 levels has certain predictive value for the prognosis of advanced NSCLC patients.

Key words:Carcinoma,non-small-cell lung,miR-499,miR-362,Prognosis

倪国英, 黄骞, 梁洪享, 杨志勇, 丁颖丽. 晚期非小细胞肺癌患者血清miR-499、miR-362水平变化及与预后的关系分析[J]. 国际肿瘤学杂志, 2024, 51(8): 487-492.

Ni Guoying, Huang Qian, Liang Hongxiang, Yang Zhiyong, Ding Yingli. Analysis of changes in serum miR-499 and miR-362 levels and their relationship with prognosis in advanced NSCLC patients[J]. Journal of International Oncology, 2024, 51(8): 487-492.

图/表5

一般资料	NSCLC组（n=103）	对照组（n=100）	χ²/t值	P值
性别
男	67	77	0.42	0.120
女	36	23
年龄（岁）	51.73±6.95	50.26±6.34	0.79	0.250
体质量指数（kg/m²）	21.86±3.15	22.01±3.18	0.45	0.648

表1

组别	miR-499	miR-362
NSCLC组（n=103）	0.34±0.10	1.13±0.27
对照组（n=100）	1.25±0.21	0.63±0.15
t值	18.26	16.32
P值	<0.001	<0.001

表2

表3

不同临床特征晚期NSCLC患者血清miR-499、miR-362水平对比（$\bar{x}±s$）"

临床特征	例数	miR-499	t值	P值	miR-362	t值	P值
年龄(岁)
<50	39	0.34±0.09	0.26	0.514	1.12±0.26	0.80	0.513
≥50	64	0.33±0.08	0.26	0.514	1.13±0.28	0.80	0.513
性别
男	67	0.33±0.08	0.76	0.312	1.13±0.27	0.83	0.269
女	36	0.33±0.09	0.76	0.312	1.13±0.28	0.83	0.269
分化程度
低分化	40	0.23±0.06	11.12	<0.001	1.52±0.33	16.35	<0.001
中高分化	63	0.35±0.08	11.12	<0.001	1.11±0.26	16.35	<0.001
TNM分期
ⅢB	48	0.34±0.09	13.64	0.002	1.12±0.27	8.73	0.010
Ⅳ	55	0.24±0.06	13.64	0.002	1.45±0.31	8.73	0.010
淋巴结转移
有	35	0.22±0.06	10.02	0.003	1.50±0.31	9.65	0.004
无	68	0.35±0.09	10.02	0.003	1.13±0.28	9.65	0.004

表3

组别	miR-499	miR-362
死亡组（n=77）	0.24±0.06	1.54±0.32
生存组（n=26）	0.35±0.09	1.08±0.21
t值	8.06	8.67
P值	0.006	0.005

表4

图1

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