Hsa_circ_0041150 可作为一线化疗方案治疗的小细胞肺癌患者化疗耐药监测的新型生物标志物。
Hsa_circ_0041150 serves as a novel biomarker for monitoring chemotherapy resistance in small cell lung cancer patients treated with a first-line chemotherapy regimen.
机构信息
Cheeloo College of Medicine, Shandong University, Jinan, China.
The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.
出版信息
J Cancer Res Clin Oncol. 2023 Nov;149(17):15365-15382. doi: 10.1007/s00432-023-05317-6. Epub 2023 Aug 28.
PURPOSE
To explore the potential of circRNAs as biomarkers in non-invasive body fluids for monitoring chemotherapy resistance in SCLC patients.
METHODS
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.
RESULTS
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.
CONCLUSION
Thus, EVs hsa_circ_0041150 holds promise as a biomarker for monitoring chemotherapy resistance in SCLC patients.
目的
探索环状 RNA（circRNA）作为小细胞肺癌（SCLC）患者化疗耐药监测的非侵入性体液生物标志物的潜力。
方法
使用转录组测序、Sanger 测序、放线菌素 D 处理和核糖核酸酶 R 测定筛选和表征 circRNAs。我们的研究纳入了 174 名参与者，所有化疗耐药患者（n=54）在疾病稳定和进展两个时间点采集血清样本。我们使用超速离心、透射电子显微镜、纳米流式细胞术和 Western blot 分析从患者中分离和鉴定血清细胞外囊泡（EVs）。通过实时定量聚合酶链反应（qRT-PCR）测定血清和血清 EVs circRNAs 的表达水平。通过增殖测定、划痕试验、Transwell 测定和顺铂耐药测定等各种测定评估 circRNA 对 SCLC 细胞功能的影响。
结果
发现 hsa_circ_0041150 在化疗耐药 SCLC 细胞中上调，并在促进增殖、侵袭、迁移和顺铂耐药中发挥作用。此外，当 SCLC 患者在一线化疗方案后发生耐药时，血清和血清 EVs 中 hsa_circ_0041150 的表达水平增加。当与 NSE 联合使用时，化疗耐药的监测敏感性（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 进展到 PD 的时间显著相关，耐药后 hsa_circ_0041150 水平升高更有可能导致化疗耐药。此外，hsa_circ_0041150 在监测 SCLC 患者从初始诊断到化疗耐药的进展方面具有重要的潜在价值。
结论
因此，EVs hsa_circ_0041150 有望成为监测 SCLC 患者化疗耐药的生物标志物。
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