小细胞肺癌（Small Cell Lung Cancer, SCLC）的预后非常差，因为大多数情况最初被诊断为广泛转移性疾病，并且伴随血行转移。因此，SCLC的早期诊断非常重要，可能会改善预后。为了研究早期诊断SCLC的可行性，我们检查了从SCLC患者获得的血清中存在的外泌体微小RNA（miRNA）。首先，我们分离了从SCLC患者和健康个体的血清中获得的外泌体，并利用粒径和蛋白标记进行了表征。此外，我们进行了miRNA阵列以确定SCLC特异的外泌体miRNA。其次，我们进一步验证了获得的miRNA，使用了大规模队列。最后，通过曲线下面积（AUC）评估了SCLC的诊断能力，并通过验证的miRNA验证了细胞内mRNA变化模式。根据miRNA阵列结果，我们根据p值和前10个差异表达基因选择了51个miRNA，使用定量逆转录聚合酶链反应验证了25个miRNA。这25个miRNA在大规模队列中进行了进一步验证。其中，有7个miRNA显示出显著差异。此外，6个miRNA（miR-3565，miR-3124-5p，miR-200b-3p，miR-6515，miR-3126-3p和miR-9-5p）上调，1个miRNA（miR-92b-5p）下调。每个miRNA集合的AUC值介于0.64和0.76之间，但是3个miRNA（miR-200b-3p，miR-3124-5p和miR-92b-5p）的联合应用显著提高了诊断价值（AUC=0.93）。基因本体分析显示，这3个miRNA面板与各种癌基因途径和神经系统发育相关。当这3个miRNA引入细胞时，总mRNA表达的变化强烈提示存在肺部疾病，包括肺癌。此外，这3个miRNA面板与更差的预后显著相关，尽管尚未验证个体miRNA作为预后标志物。我们的研究鉴定了SCLC特异的外泌体miRNA，而3个miRNA面板（miR-200b-3p，miR-3124-5p和miR-92b-5p）可能作为SCLC的诊断和预后标志物。© 2023. Yumed Inc. and BioMed Central Ltd., part of Springer Nature.

Small cell lung cancer (SCLC) has an exceptionally poor prognosis; as most of the cases are initially diagnosed as extensive disease with hematogenous metastasis. Therefore, the early diagnosis of SCLC is very important and may improve its prognosis.To investigate the feasibility of early diagnosis of SCLC, we examined exosomal microRNAs (miRNAs) present in serum obtained from patients with SCLC. First, exosomes were isolated in serum from patients with SCLC and healthy individuals and were characterized using particle size and protein markers. Additionally, miRNA array was performed to define SCLC-specific exosomal miRNAs. Second, the obtained miRNAs were further validated employing a large cohort. Finally, the ability to diagnose SCLC was estimated by area under the curve (AUC), and intracellular mRNA change patterns were verified through validated miRNAs.From the miRNA array results, we selected 51-miRNAs based on p-values and top 10 differentially expressed genes, and 25-miRNAs were validated using quantitative reverse transcription-polymerase chain reaction. The 25-miRNAs were further validated employing a large cohort. Among them, 7-miRNAs showed significant differences. Furthermore, 6-miRNAs (miR-3565, miR-3124-5p, miR-200b-3p, miR-6515, miR-3126-3p and miR-9-5p) were up-regulated and 1-miRNA (miR-92b-5p) was down-regulated. The AUC value of each miRNA sets between 0.64 and 0.76, however the combined application of 3-miRNAs (miR-200b-3p, miR-3124-5p and miR-92b-5p) remarkably improved the diagnostic value (AUC = 0.93). Gene ontology analysis revealed that the 3-miRNA panel is linked to various oncogene pathways and nervous system development. When the 3-miRNAs were introduced to cells, the resulting changes in total mRNA expression strongly indicated the presence of lung diseases, including lung cancer. In addition, the 3-miRNA panel was significantly associated with a poorer prognosis, although individual miRNAs have not been validated as prognostic markers.Our study identified SCLC-specific exosomal miRNAs, and the 3-miRNAs panel (miR-200b-3p, miR-3124-5p and miR-92b-5p) may serve as a diagnostic and prognostic marker for SCLC.© 2023. Yumed Inc. and BioMed Central Ltd., part of Springer Nature.