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.
Highlights
Prostate cancer (PC) is the most common non-cutaneous cancer and the second leading cause of cancer-associated deaths among men.[1]
20 men confirmed the absence of PC; 20 men were in CPG1; 20 men were in CPG5, and 20 men presented with established metastatic disease (Supplementary Table S1)
PTN is a secreted growth factor with diverse functions related to tumour growth, angiogenesis and metastasis.[12,13,14]
Summary
Prostate cancer (PC) is the most common non-cutaneous cancer and the second leading cause of cancer-associated deaths among men.[1]. PSA cannot distinguish between low-risk patients who do not need treatment and clinically significant disease, which will have a poor prognosis if not treated.[2] Many screening studies using PSA have shown that while more cancers can be found, many of these are indolent and are overtreated. The use of PSA as a screening test remains highly controversial.[3] Instead, the focus has shifted to the development of biomarkers for clinically significant disease. Significant progress has been made in developing new and improved biomarkers such as the prostate health index, and the STHLM3 test.[4] Urine biomarkers such as PCA3 and Select Mdx have shown the potential to improve PC detection specificity. Significant improvements over PSA alone, these tests still identify many cancers that may not cause harm if un-detected
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