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The diagnostic potential of two exosome-derived circRNAs for papillary thyroid cancer

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Abstract

Background

As a critical component of exosomes, circular RNAs (circRNAs) have shown great value in cancer diagnosis. This study aimed to identify circRNAs in exosomes for the diagnosis of PTC (papillary thyroid carcinoma).

Methods

We selected hsa_circ_0082002 and hsa_circ_0003863 based on circRNA microarray. The levels of exosomal hsa_circ_0082002 and hsa_circ_0003863 in the sera of healthy control (n = 68), benign thyroid tumors (n = 60), and PTC without and with Hashimoto’s thyroiditis (n = 164) were quantified by qPCR (quantitative polymerase chain reaction). Receiver operating characteristic analyses were conducted to evaluate the diagnostic sensitivity and specificity. Bioinformatics databases were used to predict the microRNAs and proteins binding with hsa_circ_0082002 and hsa_circ_0003863.

Results

The levels of exosomal hsa_circ_0082002 and hsa_circ_0003863 were positively associated and statistically increased in PTC compared to healthy and benign thyroid tumors. Intriguingly, higher levels of exosomal hsa_circ_0082002 and hsa_circ_0003863 were positively correlated with lymph node metastasis and vascular invasion in PTC. Further stability tests show that exosomal hsa_circ_0082002 and hsa_circ_0003863 could exist stably in sera treated by several freeze–thaw cycles at -20 °C and with a storage time shorter than 24 h at 4 °C. Furthermore, hsa_circ_0082002 and hsa_circ_0003863 were predicted to interact with microRNAs and proteins, suggesting that hsa_circ_0082002 and hsa_circ_0003863 might contribute to the occurrence and progression of PTC through interacting with microRNAs and RNA binding proteins.

Conclusion

Collectively, we identified two PTC-related circRNAs incorporated in exosomes and uncovered their potential as tumor markers to diagnose PTC, in particular, more aggressive PTC.

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Availability of data and material

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

PTC:

Papillary thyroid carcinoma

circRNA:

Circular RNA

ROC:

Receiver operator characteristic

AUC:

Area under the ROC curve

qPCR:

Quantitative polymerase chain reaction

FNAB:

Fine needle aspiration biopsy

PET:

Positron emission tomography

CT:

Computed tomography

miRNA:

MicroRNA

lncRNA:

Long non-coding RNA

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Acknowledgements

We thank Prof. Junming Guo for providing us with the qPCR instrument.

Funding

This study is supported by the Natural Science Foundation of Ningbo (2023J322, 2023J077, and 2021J313); the Research Foundation of Ningbo No.2 Hospital (2022HMK40); the Young Technical Backbone Talent of Health in Ningbo; the Zhu Xiushan Talent Award Fund of Ningbo NO.2 Hospital (2021HMYQ06); the Project of NINGBO Leading Medical & Health Discipline (2022-F18).

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Authors and Affiliations

  1. Department of Thyroid Surgery, Ningbo No. 2 Hospital, 41 Xibei Road, Haishu, Ningbo, 315000, ZJ, China

    Lei Dai, Yingchun Wang, Qi Le & Xianjiang Wu

  2. Department of Surgery, Xiangshan County Red Cross Taiwan Compatriots Hospital Medical and Health Group General Hospital, Ningbo, 315700, China

    Weibin Hu

  3. Department of Biochemistry and Molecular Biology, the Health Science Center of Ningbo University, 818 Fenghua Road, Ningbo, ZJ, China

    Han Jiang & Xiaodan Meng

  4. Zhejiang Provincial Key Laboratory of Pathophysiology, the Health Science Center of Ningbo University, Ningbo, 315211, China

    Han Jiang & Xiaodan Meng

Authors
  1. Lei Dai
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  2. Weibin Hu
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  3. Han Jiang
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  4. Yingchun Wang
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  5. Qi Le
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  6. Xianjiang Wu
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  7. Xiaodan Meng
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Contributions

Study design and supervision: LD, XW, XM. Development of methodology: LD, WH, HJ. Acquisition of data (acquired and managed patients): LD, YW, QL. Analysis and interpretation of data (e.g., statistical analysis, biostatistics): LD. Writing, review, and/or revision of the manuscript: LD, XW, XM.

Corresponding authors

Correspondence to Xianjiang Wu or Xiaodan Meng.

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Conflict of interest

The authors declare no competing interest.

Ethics approval and consent to participate

This study was performed following the Declaration of Helsinki. Written informed consent was obtained from all patients, and the study was approved by the ethics committee (the Clinical Research Ethics Committee of Ningbo No.2 Hospital) with the number of. YJ-NBEY-KY-2021-181-01.

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Dai, L., Hu, W., Jiang, H. et al. The diagnostic potential of two exosome-derived circRNAs for papillary thyroid cancer. Int J Clin Oncol 28, 1461–1474 (2023). https://doi.org/10.1007/s10147-023-02400-3

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  • DOI: https://doi.org/10.1007/s10147-023-02400-3

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