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检测血清外泌体中的miR-128-3p和miR-33a-5p作为非小细胞肺癌辅助诊断生物标志物的研究

A test of miR-128-3p and miR-33a-5p in serum exosome as biomarkers for auxiliary diagnosis of non-small cell lung cancer.

作者信息

Li Mengxing, Liu Tao, Cheng Wen, Jin Hai, Wang Xiaowei

机构信息

Department of Thoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.

出版信息

J Thorac Dis. 2023 May 30;15(5):2616-2626. doi: 10.21037/jtd-23-398. Epub 2023 May 23.

Abstract

BACKGROUND

Lung cancer is the malignant tumor with the highest incidence and mortality rate in the world today, and non-small cell lung cancer (NSCLC) is its most common type. However, there is still a paucity of specific tumor markers for lung cancer screening. Herein, we detected and compared the levels of miR-128-3p and miR-33a-5p in serum exosomes of NSCLC patients and healthy volunteers, with the aim of identifying suitable exosomal microRNAs (miRNAs) as tumor biomarkers, and explored their value in the auxiliary diagnosis of NSCLC.

METHODS

All participants were recruited from September 1, 2022 to December 30, 2022, and met the inclusion criteria. The case group included 20 patients with lung nodules who were highly suspected of having lung cancer (two cases were excluded). A total of 18 healthy volunteers (control group) were also enrolled. Blood samples were collected in both the case group before surgery and in the control group. Quantitative real-time polymerase chain reaction method was used to detect the expression of miR-128-3p and miR-33a-5p in serum exosomes. The main indicators of statistical analysis included the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity.

RESULTS

Compared with the healthy control group, the NSCLC case group had significantly lower expression levels of serum exosome miR-128-3p and miR-33a-5p (P<0.01, P<0.001), and there was a significant positive correlation between the two exosome miRNAs (r=0.848, P<0.01). The AUC values of miR-128-3p alone and miR-33a-5p alone in distinguishing case group and control group were 0.789 [95% confidence interval (CI): 0.637-0.940; sensitivity: 61.1%; specificity: 94.4%; P=0.003] and 0.821 (95% CI: 0.668-0.974; sensitivity: 77.8%; specificity: 83.3%; and P=0.001), respectively. The combination of miR-128-3p and miR-33a-5p had an AUC of 0.855 (95% CI: 0.719-0.991; P<0.001) for distinguishing case group and control group, which was greater than the AUC values of miR-128-3p alone and miR-33a-5p alone (cut-off value: 0.034; sensitivity: 83.3%; and specificity: 88.9%). However, there was no significant difference in the AUC among these three groups (P>0.05).

CONCLUSIONS

Serum exosome miR-128-3p and miR-33a-5p showed good performance in NSCLC screening and may be used as new biomarkers for large-scale NSCLC screening.

摘要

背景

肺癌是当今世界发病率和死亡率最高的恶性肿瘤,非小细胞肺癌(NSCLC)是其最常见的类型。然而,用于肺癌筛查的特异性肿瘤标志物仍然匮乏。在此,我们检测并比较了NSCLC患者和健康志愿者血清外泌体中miR-128-3p和miR-33a-5p的水平,旨在鉴定合适的外泌体微小RNA(miRNA)作为肿瘤生物标志物,并探讨它们在NSCLC辅助诊断中的价值。

方法

所有参与者于2022年9月1日至2022年12月30日招募,并符合纳入标准。病例组包括20例高度怀疑患有肺癌的肺结节患者(排除2例)。共纳入18名健康志愿者(对照组)。病例组在手术前和对照组均采集血样。采用定量实时聚合酶链反应法检测血清外泌体中miR-128-3p和miR-33a-5p的表达。统计分析的主要指标包括受试者操作特征曲线下面积(AUC)、敏感性和特异性。

结果

与健康对照组相比,NSCLC病例组血清外泌体miR-128-3p和miR-33a-5p的表达水平显著降低(P<0.01,P<0.001),且两种外泌体miRNA之间存在显著正相关(r=0.848,P<0.01)。单独的miR-128-3p和单独的miR-33a-5p区分病例组和对照组的AUC值分别为0.789 [95%置信区间(CI):0.637-0.940;敏感性:61.1%;特异性:94.4%;P=0.003]和0.821(95% CI:0.668-0.974;敏感性:77.8%;特异性:83.3%;P=0.001)。miR-128-3p和miR-33a-5p联合用于区分病例组和对照组的AUC为0.855(95% CI:0.719-0.991;P<0.001),大于单独的miR-128-3p和单独的miR-33a-5p的AUC值(截断值:0.034;敏感性:83.3%;特异性:88.9%)。然而,这三组之间的AUC无显著差异(P>0.05)。

结论

血清外泌体miR-128-3p和miR-33a-5p在NSCLC筛查中表现良好,可能用作大规模NSCLC筛查的新生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3837/10267929/80f4ddb36e1a/jtd-15-05-2616-f1.jpg

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