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

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.

Small-Cell Lung Cancer: Is Liquid Biopsy a New Tool Able to Predict the Efficacy of Immunotherapy?

“…Zhang and co-authors demonstrated that it promotes both cancer progression and cisplatin resistance in SCLC models, suggesting this circRNA has a role as a biomarker for monitoring chemotherapy resistance in patients treated with cisplatin-based chemotherapy. They showed its higher value as a diagnostic biomarker with respect to traditional cancerassociated markers such as CA125, CA211, and ProGRP in SCLC and its modulation in the function of treatment response, passing from an already higher value present in patients compared to healthy people, which tends to decrease when the patient responds to therapy and then rises again when resistance appears [81].…”

“…[80] Extracellular vesicles hsa_circ_0041150 / EVs hsa_circ_0041150 could be a biomarker for monitoring chemotherapy resistance in SCLC patients. [81] NLRP6 / By activating NLRP6, SCLC-derived exosomes cause the immunosuppression of distant macrophages, promoting systemic metastasis.…”