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Molecular Diagnostics

Discovery of PTN as a serum-based biomarker of pro-metastatic prostate cancer

Abstract

Distinguishing clinically significant from indolent prostate cancer (PC) is a major clinical challenge. We utilised targeted protein biomarker discovery approach to identify biomarkers specific for pro-metastatic PC. Serum samples from the cancer-free group; Cambridge Prognostic Group 1 (CPG1, low risk); CPG5 (high risk) and metastatic disease were analysed using Olink Proteomics panels. Tissue validation was performed by immunohistochemistry in a radical prostatectomy cohort (n = 234). We discovered that nine proteins (pleiotrophin (PTN), MK, PVRL4, EPHA2, TFPI-2, hK11, SYND1, ANGPT2, and hK14) were elevated in metastatic PC patients when compared to other groups. PTN levels were increased in serum from men with CPG5 compared to benign and CPG1. High tissue PTN level was an independent predictor of biochemical recurrence and metastatic progression in low- and intermediate-grade disease. These findings suggest that PTN may represent a novel biomarker for the presence of poor prognosis local disease with the potential to metastasise warranting further investigation.

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Fig. 1: Discovery of PTN as a potential serum-based biomarker for clinically significant prostate cancer through high-multiplex immunoassays.

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Acknowledgements

Opinions, interpretations, conclusions and recommendations are those of the authors and not necessarily endorsed by the US Army and the funding agencies. V.J.G. acknowledges infrastructure funding from CRUK Cambridge Cancer Centre and the NIHR Cambridge Biomedical Campus. Samples used in the serum analysis were collected under the DIAMOND study ethics REC 03/018.

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Authors

Contributions

S.L., J.D.B., V.J.G. and T.S. designed research. S.L., M.S., E.-C.H., C.A.Z., F.G.-M., R.N., K.K., M.A.R., M.A., S.J.P., C.M., A.G., J.D.B., V.J.G. and T.S. performed research. J.D.B., V.J.G. and T.S. contributed reagents/tools. S.L., M.S., E.-C.H., C.A.Z., F.G.-M., R.N., K.K., M.A.R., M.A., S.J.P., C.M., A.G., J.D.B., V.J.G. and T.S. analysed the data. S.L., S.J.P., J.D.B., V.J.G. and T.S. wrote the manuscript.

Corresponding authors

Correspondence to Vincent J. Gnanapragasam or Tanya Stoyanova.

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Ethics approval and consent to participate

The CPGs are routinely used to classify all men recruited into the Cambridge Urological Biorepository and all men consent to participate (DIAMOND study CI V.J.G., Ethics 03/018).

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Not applicable.

Data availability

All data in this study are included as Supplementary Tables and Figures. Any additional information is available upon request.

Competing interests

The authors declare no competing interests.

Funding information

This work was supported by the Canary Foundation and the CRUK Cambridge-Canary Center Joint Pump Priming Award. T.S. is supported by the Canary Foundation, National Institutes of Health/National Cancer Institute (NCI) R37CA240822, R01CA244281 and R03CA230819. M.A.R. is supported by the US Army Medical Research Acquisition Activity, through the CDMRP Award No. W81XWH1810141. J.D.B. is supported by NIH CA229933 and NIH CA196387.

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Liu, S., Shen, M., Hsu, EC. et al. Discovery of PTN as a serum-based biomarker of pro-metastatic prostate cancer. Br J Cancer 124, 896–900 (2021). https://doi.org/10.1038/s41416-020-01200-0

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