Endocrine Abstracts

Prostate cancer (PCa) is one of the leading causes of cancer deaths among men population worldwide. This tumour pathology is commonly diagnosed through the determination of serum PSA levels. However, the diagnostic capability of PSA dramatically drops when considering patients with PSA levels lower than 10 ng/ml, the so-called “grey-zone”¹. Therefore, additional non-invasive diagnostic biomarkers are urgently needed to substitute/complement PSA. In this sense, the ghrelin system has been found to be altered in PCa, whether the splicing variant In1-ghrelin plays a relevant role². Additionally, it has been reported that serum In1-ghrelin levels are elevated in PCa patients². However, the potential utility of urine In1-ghrelin levels in PCa diagnosis has not been explored. Therefore, this study aimed to analyse the diagnostic utility of urine In1-ghrelin levels in PCa. Herein, In1-ghrelin levels were determined by RIA in urine from an ample cohort of patients with PSA in the grey-zone (n = 600). Our results showed that urine In1-ghrelin levels were higher in PCa patients vs. patients with a suspect of PCa but negative biopsy result, whereas serum PSA levels did not differ between these two groups. Moreover, In1-ghrelin added significant diagnostic value to a clinical model consisting of age, suspicious digital rectal examination (DRE), previous biopsy, and PSA levels. Consistently, high In1-ghrelin levels [OR = 2.93, P < 0.0001], but not PSA levels [OR = 1.09, P > 0.05], were associated to an increased PCa risk. Moreover, urine In1-ghrelin levels were linked to PCa-aggressiveness parameters (e.g. tumour stage, lymphovascular invasion). Furthermore, several metabolic-factors [e.g. body-mass index (BMI), diabetes mellitus (DM), glucose, and insulin levels] were strongly correlated to urine In1-ghrelin levels as well as associated with PCa risk. Finally, a multivariate model consisting of metabolic [i.e. BMI, waist-circumference, DM, glucose, insulin, cholesterol, and Ghrelyn-O-acyl transferase (GOAT) levels] and clinical (i.e. age, DRE, previous biopsy, and PSA levels) variables, and In1-ghrelin levels showed high specificity and sensitivity to diagnose PCa in our patients cohort (AUC = 0.741, P < 0.0001). Taken together, our results pose the potential for urine In1-ghrelin levels as a useful clinical diagnostic and prognostic biomarker of PCa in patients with PSA in the grey-zone.

References

1. Ross T, et al. Clarifying the PSA grey zone: The management of patients with a borderline PSA. Int J Clin Pract. 2016, 70(11):950–959.

2. Hormaechea-Agulla D, et al. The oncogenic role of the In1-ghrelin splicing variant in prostate cancer aggressiveness. Mol Cancer. 2017, 16(1):146.

Fundings

ISCIII (PI16–00264), MINECO (PID2019–105564RB-100/FPU18–02485/FPU16–06190), Junta de Andalucía (BIO-0139), CIBERobn.