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Genetics and Genomics

Plasma extracellular vesicle circRNA signature and resistance to abiraterone in metastatic castration-resistant prostate cancer

British Journal of Cancer volume 128, pages 1320–1332 (2023)Cite this article

Subjects

Abstract

Background

We aimed to develop and validate a plasma extracellular vesicle circular RNA (circRNA)-based signature that can predict overall survival (OS) in first-line abiraterone therapy for metastatic castration-resistant prostate cancer (mCRPC) patients.

Methods

In total, 582 mCRPC patients undergoing first-line abiraterone therapy from four institutions were sorted by three phases. In the discovery phase, 30 plasma samples from 30 case-matched patients with or without early progression were obtained to generate circRNA expression profiles using RNA sequencing. In the training phase, differentially expressed circRNAs were examined using digital droplet PCR in a training cohort (n = 203). The circRNA signature was constructed using a least absolute shrinkage and selection operator Cox regression to predict OS. In the validation phase, the prognostic ability of this signature was prospectively validated in two external cohorts (Cohort I, n = 183; Cohort II, n = 166).

Results

We developed a five-circRNA signature, based on circCEP112, circFAM13A, circBRWD1, circVPS13C and circMACROD2, which successfully stratified patients into high-risk and low-risk groups. The prognostic ability of this signature was prospectively validated in two external cohorts (P < 0.0001, P < 0.0001). Patients with high-risk scores had shorter OS than patients with low-risk scores.

Conclusion

This five-circRNA signature is a reliable predictor of OS for mCRPC patients undergoing abiraterone.

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Fig. 1: Study flow.
Fig. 2: Construction of the five-circRNA signature.
Fig. 3: CircRNA risk-score analysis of 203 mCRPC patients in the training cohort.
Fig. 4: CircRNA risk-score analysis of 183 mCRPC patients in Cohort I.
Fig. 5: CircRNA risk-score analysis of 166 mCRPC patients in Cohort II.
Fig. 6: Best PSA responses, Kaplan–Meier curves of progression-free survival and overall survival according to the five-circRNA signature.
Fig. 7: Discriminatory performance of the five-circRNA signature using receiver operating characteristic analyses in the training and validation cohorts.
Fig. 8: Discriminatory performance of the five-circRNA signature using decision curve analyses in the training and validation cohorts.

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Data availability

All data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank all patients involved in this study.

Funding

This study was funded by National Natural Science Foundation of China (81472383, 81502206, 81772753, 81972419), Guangdong Provincial Natural Science Foundation of China (2014A030313088, 2017A030313478), Guangdong Provincial Science and Technology Provincial Science and Technology Foundation of China (2016A020215073), Guangzhou Science and Technology Foundation of China (201804010324), and the Fundamental Research Funds for the Central Universities (17ykzd21).

Author information

Author notes

  1. These authors contributed equally: Wen Tao, Zi-Huan Luo, Ya-Di He, Bang-Yu Wang.

Authors and Affiliations

  1. Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, 510630, Guangzhou, China

    Wen Tao, Zi-Huan Luo, Xin Gao & Liao-Yuan Li

  2. Center of Health Management, The Third Affiliated Hospital, Sun Yat-sen University, 510630, Guangzhou, China

    Ya-Di He & Xiu-Mei Tang

  3. Department of Breast Surgery, The Third Affiliated Hospital, Sun Yat-sen University, 510630, Guangzhou, China

    Bang-Yu Wang

  4. Department of Urology, Foshan First Municipal People’s Hospital, Sun Yat-sen University, 528000, Foshan, China

    Tao-Lin Xia

  5. Department of Urology, The First Affiliated Hospital, University of South China, 421000, Hengyang, China

    Wei-Ming Deng

  6. Department of Urology, The First Affiliated Hospital, Hainan Medical University, 570102, Haikou, China

    Ling-Xiao Zhang

  7. Department of Radiology, The Third Affiliated Hospital, Sun Yat-sen University, 510630, Guangzhou, China

    Zhan-Ao Meng

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Contributions

XG and L-YL: conceptualisation. WT, Z-HL, Y-DH and B-YW: methodology and writing manuscript original draft. WT, Z-HL, Y-DH and B-YW: formal analysis. WT, T-LX, W-MD, L-XZ, X-MT and Z-AM: data collection and curation. X-MT and Z-AM: biological sample analysis and interpretation of these data. All authors: reviewing and editing the manuscript. XG and L-YL: supervision. XG and L-YL: project administration. L-YL and Y-DH: funding acquisition.

Corresponding authors

Correspondence to Xin Gao or Liao-Yuan Li.

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This study was conducted in compliance and in accordance with the Declaration of Helsinki. This study was approved by the Institutional Ethical Review Board at The Third Affiliated Hospital of Sun Yat-sen University, and signed informed consent was obtained for all subjects included in the study.

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Tao, W., Luo, ZH., He, YD. et al. Plasma extracellular vesicle circRNA signature and resistance to abiraterone in metastatic castration-resistant prostate cancer. Br J Cancer 128, 1320–1332 (2023). https://doi.org/10.1038/s41416-023-02147-8

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