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

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

Racial and Sociodemographic Differences of Semen Parameters Among US Men Undergoing a Semen Analysis

Objective: To characterize sociodemographic differences in semen parameters among US men undergoing a semen analysis. Materials and Methods: Men who provided a semen sample were identified from insurance claims between 2007 and 2016. Differences in semen parameters were characterized according to age, race, education, and region. Mean semen parameters and proportions of men with suboptimal parameters were compared and risks of oligospermia and azoospermia were assessed by logistic regression. Results: Of the 7263 men included, most men were white (55.1%), Hispanic (20.2%), or Asian (10.2%). Asians had the highest mean semen concentrations (69.2 × 106/mL), whereas blacks had the lowest (51.3 × 106/mL). Men from the Midwest were more likely to have oligospermia (odds ratio [OR] 1.62; 95% confidence interval [CI] 1.34-1.94), whereas men from the West were less likely (OR 0.82; 95% CI 0.82-0.94) when compared with men from South. An association between education and sperm concentration was observed. For example, men with a high school diploma or less were more likely to have oligospermia (OR 1.09; 95% CI 0.95-1.26), whereas men with at least a bachelor degree were less likely (OR 0.87; 95% CI 0.76-1.0) when compared with men with less than a bachelor degree. Conclusion: As we observed differences in semen quality based on sociodemographic factors, these findings may have clinical implications as relying on a single reference value when guiding infertile couples may be problematic given these variations. Further work is warranted to understand the etiology of such differences and determine if different normative reference values may apply for different populations

Trop2 is a driver of metastatic prostate cancer with neuroendocrine phenotype via PARP1

Resistance to androgen deprivation therapy, or castration-resistant prostate cancer (CRPC), is often accompanied by metastasis and is currently the ultimate cause of prostate cancer-associated deaths in men. Recently, secondary hormonal therapies have led to an increase of neuroendocrine prostate cancer (NEPC), a highly aggressive variant of CRPC. Here, we identify that high levels of cell surface receptor Trop2 are predictive of recurrence of localized prostate cancer. Moreover, Trop2 is significantly elevated in CRPC and NEPC, drives prostate cancer growth, and induces neuroendocrine phenotype. Overexpression of Trop2 induces tumor growth and metastasis while loss of Trop2 suppresses these abilities in vivo. Trop2-driven NEPC displays a significant up-regulation of PARP1, and PARP inhibitors significantly delay tumor growth and metastatic colonization and reverse neuroendocrine features in Trop2-driven NEPC. Our findings establish Trop2 as a driver and therapeutic target for metastatic prostate cancer with neuroendocrine phenotype and suggest that high Trop2 levels could identify cancers that are sensitive to Trop2-targeting therapies and PARP1 inhibition