Duan Xiaotong, Qiao Simiao, Li Dianhe, Li Shangbiao, Zheng Zhihao, Wang Qin, Zhu Xiaoxia
Department of Radiation Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Front Genet. 2021 Jul 9;12:673926. doi: 10.3389/fgene.2021.673926. eCollection 2021.
Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancers. This study aimed to discover the potential miRNA biomarkers for early detection of NSCLC.
Total circulating miRNAs were extracted from six patients and six volunteers and run on the miRNA chip. The differentially expressed miRNAs acquired by data mining were intersected with chip results, and qRT-PCR were carried out. Then the differentially miRNAs were validated by using a validation cohort (120 participants). ROC curves were established to evaluate the diagnostic efficacy of the differentially circulating miRNAs. The target genes of the differential miRNAs were identified using the miRTarBase database, and follow-up GO and KEGG enrichment analysis were conducted.
We identified 577 miRNA which screened according to the criteria (fold change > 2 and value < 0.05). Among them, seven circulating miRNAs passed additional filtering based on data mining. These miRNAs were further validated in the training and validation cohort. miR-492, miR-590-3p, and miR-631 were differentially expressed in the patients' serum, and the area under the ROC curve (AUC) values of these miRNAs were 0.789, 0.792, and 0.711, respectively. When using them as a combination to discriminate healthy volunteers from patients, the AUC reached 0.828 (95% CI, 0.750-0.905, = 0.000) with a sensitivity of 86.7% and specificity of 71.7%. The follow-up enrichment analysis showed that target genes of three miRNA were associated with tumorigenesis and progression, such as cell cycle and P53 signaling pathway.
The combination of miR-492, miR-590-3p, and miR-631 can be utilized to distinguish healthy individuals and early-stage NSCLC patients.
The combination of miR-492, miR-590-3p, and miR-631 might be a promising serum biomarker in patients for the early diagnosis of NSCLC.
非小细胞肺癌（NSCLC）约占肺癌的85%。本研究旨在发现用于NSCLC早期检测的潜在miRNA生物标志物。
从6例患者和6名志愿者中提取循环总miRNA，并在miRNA芯片上进行检测。通过数据挖掘获得的差异表达miRNA与芯片结果进行比对，并进行qRT-PCR。然后使用验证队列（120名参与者）对差异miRNA进行验证。绘制ROC曲线以评估差异循环miRNA的诊断效能。使用miRTarBase数据库鉴定差异miRNA的靶基因，并进行后续的GO和KEGG富集分析。
我们鉴定出577个根据标准筛选的miRNA（倍数变化>2且P值<0.05）。其中，7个循环miRNA基于数据挖掘通过了进一步筛选。这些miRNA在训练队列和验证队列中进一步得到验证。miR-492、miR-590-3p和miR-631在患者血清中差异表达，这些miRNA的ROC曲线下面积（AUC）值分别为0.789、0.792和0.711。当将它们联合用于区分健康志愿者和患者时，AUC达到0.828（95%CI，0.750-0.905，P = 0.000），灵敏度为86.7%，特异性为71.7%。后续富集分析表明，三种miRNA的靶基因与肿瘤发生和进展相关，如细胞周期和P53信号通路。
miR-492、miR-590-3p和miR-631的联合可用于区分健康个体和早期NSCLC患者。
miR-492、miR-590-3p和miR-631的联合可能是NSCLC患者早期诊断中有前景的血清生物标志物。
