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

Yang Zhang; Fengmei Chao; Lihua Lv; Ming Li; Zuojun Shen

doi:10.1007/s00432-023-05317-6

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

J Cancer Res Clin Oncol. 2023 Nov;149(17):15365-15382. doi: 10.1007/s00432-023-05317-6. Epub 2023 Aug 28.

Authors

Yang Zhang^{1

2

3

4}, Fengmei Chao⁵, Lihua Lv^{3

4}, Ming Li^{6

7}, Zuojun Shen^{8

9

10

11}

Affiliations

¹ Cheeloo College of Medicine, Shandong University, Jinan, China.
² The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.
³ Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230031, Anhui, China.
⁴ Core Unit of National Clinical Research Center for Laboratory Medicine, Hefei, China.
⁵ Division of Life Sciences and Medicine, Department of Cancer Epigenetics Program, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230001, Anhui, China.
⁶ Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230031, Anhui, China. lm831216@ustc.edu.cn.
⁷ Core Unit of National Clinical Research Center for Laboratory Medicine, Hefei, China. lm831216@ustc.edu.cn.
⁸ Cheeloo College of Medicine, Shandong University, Jinan, China. zuojunshen@ustc.edu.cn.
⁹ The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China. zuojunshen@ustc.edu.cn.
¹⁰ Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230031, Anhui, China. zuojunshen@ustc.edu.cn.
¹¹ Core Unit of National Clinical Research Center for Laboratory Medicine, Hefei, China. zuojunshen@ustc.edu.cn.

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.

Keywords: Extracellular vesicles; Monitor chemoresistance; Small cell lung cancer; hsa_circ_0041150.

MeSH terms

Biomarkers
Cell Proliferation / genetics
Cisplatin / therapeutic use
Humans
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
MicroRNAs* / genetics
RNA, Circular / genetics
RNA, Circular / metabolism
Small Cell Lung Carcinoma* / drug therapy
Small Cell Lung Carcinoma* / genetics

Substances

RNA, Circular
Cisplatin
Biomarkers
MicroRNAs

Abstract

MeSH terms

Substances

Grants and funding