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Prostein expression on circulating tumor cells as a prognostic marker in metastatic castration-resistant prostate cancer

Prostate Cancer and Prostatic Diseases (2023)Cite this article

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Abstract

Background

Identification of emerging molecular biomarkers on circulating tumor cells (CTCs) represents an attractive feature of liquid biopsy that facilitates precision and tailored medicine in the management of metastatic castration-resistant prostate cancer (mCRPC). Prostein is an androgen-regulated transmembrane protein with high prostate specificity. Prostein-positive circulating tumor cell (CTC) was recently suggested to have diagnostic potential; however, no study has been conducted to evaluate its prognostic value in mCRPC.

Methods

CTCs from mCRPC patients were enumerated using the CellSearch System. Prostein-positive CTCs were identified by immunostaining results. The relationships between prostein expression on CTCs and PSA response rate, PSA progression-free survival (PSA-PFS), radiographic progression-free survival (PFS), and overall survival (OS) were tested by Fisher’s exact test or evaluated using Kaplan–Meier and multivariate Cox analyses.

Results

Prostein-positive CTCs were identified in 31 of 87 baseline samples from mCRPC patients and 16 of 51 samples collected at the first follow-up visit. PSA response rates were significantly lower in baseline prostein-positive patients (0%, 0/31) than in prostein-negative patients (19.6%, 11/56) (p = 0.007). The 31 prostein-positive patients had significantly shorter PSA-PFS (p < 0.001), radiographic PFS (p < 0.001), and OS (p = 0.018), compared to the 56 prostein-negative patients at baseline. The association with PSA-PFS maintained its significance (p = 0.028) in multivariate analyses. Analyzing prostein expression at the first follow-up as well as the conversion of prostein expression from baseline to follow-up samples not only confirmed the association with PSA-PFS, but also demonstrated prognostic significance with OS.

Conclusion

Our study provides the first evidence to support the potential of prostein expression on CTCs to serve as a novel prognostic marker in mCRPC patients. Future large-scale prospective studies are needed to validate our findings.

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Fig. 1: Prostein expression on CTCs in baseline blood samples and PSA response.
Fig. 2: Kaplan–Meier survival plots of mCRPC patients using baseline blood samples.
Fig. 3: Multivariate Cox analyses of associations with mCRPC outcomes using baseline blood samples.
Fig. 4: Kaplan–Meier survival plots of mCRPC patients.
Fig. 5: Multivariate Cox analyses of associations with mCRPC outcomes.

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Data availability

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

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Funding

This study was supported by National Cancer Institute grants R01CA255792, R01CA244749 and P20CA233255, the American Cancer Society Institutional Research Grant IRG-21-138-13-IRG, the Philadelphia Prostate Cancer Biome Projects, and funding from the Sidney Kimmel Cancer Center of Thomas Jefferson University. Research reported in this publication utilized the Circulating Tumor Cell Core Facility at the Sidney Kimmel Cancer Center at Jefferson Health and was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA056036. The funding agencies were not involved in the design, conduct, analysis or interpretation of the study.

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Authors and Affiliations

  1. Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Zhenchao Zhang, Rui Luo, William K. Kelly, Joshua Chen, Shane Donahue, Kevan Ip, Nathan R. Handley, William J. Tester, Miranda L. Tsang, Ronald Myers, Grace Lu-Yao, Chun Wang & Hushan Yang

  2. Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Felix J. Kim

  3. Department of Epidemiology, MD Anderson Cancer Center, Houston, TX, 77030, USA

    Jian Gu

  4. Department of Medicine, GW Cancer Center, George Washington University, Washington, DC, 20037, USA

    Jianqing Lin

  5. Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37235, USA

    Bingshan Li

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Contributions

Study concept and design: HY, CW, ZZ; Acquisition of data: ZZ, JC, SD; Analysis and interpretation of data: HY, CW, WKK, NRH, WJT; Drafting of the manuscript: ZZ, CW, JC, KI; Critical revision of the manuscript for important intellectual content: WJT, FJK, MLT; Statistical analysis: RL, JC, CW; Obtaining funding: HY, WKK, GL-Y, CW; Administrative, technical, or material support: WKK, RM, JL, JG, BL; Supervision: HY.

Corresponding authors

Correspondence to Chun Wang or Hushan Yang.

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Competing interests

HY is on the SAB of Oriomics Inc., a shareholder of Illumina, Pfizer, and Oriomics, and serves as a NIH study section reviewer. WKK is the consultant/SAB of Janssen, Bayer, and Merck-Sharpe Dome. The above reported activities were not related to the research reported in this article. All other authors did not report any competing interests related to the research reported in this article.

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Zhang, Z., Luo, R., Kelly, W.K. et al. Prostein expression on circulating tumor cells as a prognostic marker in metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis (2023). https://doi.org/10.1038/s41391-023-00762-3

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