为了探索circRNA作为SCLC患者体内非侵入性生物液体中用于监测化疗抵抗的生物标记物的潜力。我们利用转录组测序、Sanger测序、actinomycin D处理和Ribonuclease R酶切实验对circRNA进行筛选和表征。本研究共涉及174名参与者，从所有化疗抵抗患者（n = 54）在稳定疾病和进展疾病两个时间点采集血清样本。通过超速离心、透射电镜、纳米流式细胞术和西方印迹分析，我们从患者中分离并鉴定了血清胞外囊泡（EVs）。利用定量实时聚合酶链反应（qRT-PCR）测定了血清和血清EVs circRNA的表达水平。通过增殖实验、划痕实验、转移实验和顺铂耐药实验评估了circRNA对SCLC细胞功能的影响。发现Hsa_circ_0041150在化疗抵抗的SCLC细胞中上调，并在促进增殖、侵袭、迁移和顺铂耐药方面发挥作用。此外，当SCLC患者在一线化疗方案后产生耐药时，血清和血清EVs中hsa_circ_0041150的表达水平增加。结合NSE使用时，监测化疗抵抗的敏感性（70.37%）和特异性（81.48%）显著提高。此外，hsa_circ_0041150的表达水平与从SD到PD的进展时间显著相关，药物耐药后高hsa_circ_0041150水平更容易导致化疗抵抗。此外，hsa_circ_0041150在监测SCLC患者从初诊到化疗抵抗的进展中具有有价值的潜力。因此，EVs hsa_circ_0041150在监测SCLC患者的化疗抵抗方面具有前景。©2023. 作者（们）。

To explore the potential of circRNAs as biomarkers in non-invasive body fluids for monitoring chemotherapy resistance in SCLC patients.CircRNAs were screened and characterized using transcriptome sequencing, Sanger sequencing, actinomycin D treatment, and Ribonuclease R assay. Our study involved 174 participants, and serum samples were collected from all chemotherapy-resistant patients (n = 54) at two time points: stable disease and progressive disease. We isolated and identified serum extracellular vesicles (EVs) from the patients using ultracentrifugation, transmission electron microscopy, nanoflow cytometry, and western blotting analysis. The expression levels of serum and serum EVs circRNAs were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The impact of circRNA on the function of SCLC cells was assessed through various assays, including proliferation assay, scratch assay, transwell assay, and cisplatin resistance assay.Hsa_circ_0041150 was found to be upregulated in chemoresistant SCLC cells and played a role in promoting proliferation, invasion, migration, and cisplatin resistance. Furthermore, the expression levels of hsa_circ_0041150 in serum and serum EVs increased when SCLC patients developed resistance after a first-line chemotherapy regimen. When combined with NSE, the monitoring sensitivity (70.37%) and specificity (81.48%) for chemotherapy resistance significantly improved. Moreover, the expression level of hsa_circ_0041150 showed significant associations with time to progression from SD to PD, and high hsa_circ_0041150 levels after drug resistance were more likely to cause chemotherapy resistance. Additionally, hsa_circ_0041150 demonstrated valuable potential in monitoring the progression from initial diagnosis to chemotherapy resistance in SCLC patients.Thus, EVs hsa_circ_0041150 holds promise as a biomarker for monitoring chemotherapy resistance in SCLC patients.© 2023. The Author(s).