Abstract
Abstract
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.
Funder
the Youth Fund of Anhui Cancer Hospital
the Youth Fund of the Natural Science Foundation of Anhui Province
the Fundamental Research Funds for the Central Universities
the Project of the Science and Technology Innovation of Anhui province
the Key Programs for Research and Development of Anhui Province
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,General Medicine
Cited by
5 articles.
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