Abstract
Early detection of PCa faces severe limitations as PSA displays poor‐specificity/sensitivity. As we recently demonstrated that plasma ghrelin O‐acyltransferase (GOAT)‐enzyme is significantly elevated in PCa‐patients compared with healthy‐controls, using a limited patients‐cohort, we aimed to further explore the potential of GOAT to improve PCa diagnosis using an ample patients‐cohort (n = 312) and defining subgroups (i.e. significant PCa/metastatic patients, etc.) that could benefit from this biomarker. Plasma GOAT‐levels were evaluated by ELISA in patients with (n = 183) and without (n = 129) PCa. Gleason Score ≥ 7 was considered clinically significant PCa. GOAT‐levels were higher in PCa patients vs control patients, and in those with significant PCa vs non‐significant PCa. GOAT‐levels association with the diagnoses of significant PCa was independent from traditional clinical variables (i.e. PSA/age/DRE). Remarkably, GOAT outperformed PSA in patients with PSA‐levels ranging 3‐20 ng/mL for the significant PCa diagnosis [GOAT‐AUC = 0.612 (0.531‐0.693) vs PSA‐AUC = 0.494 (0.407‐0.580)]. A panel of key variables including GOAT/age/DRE/testosterone also outperformed the same panel but with PSA [AUC = 0.720 (0.710‐0.730) vs AUC = 0.705 (0.695‐0.716), respectively]. Notably, GOAT‐levels could also represent a novel predictive biomarker of aggressiveness, as its levels are positively associated with Gleason Score and the presence of metastasis at the time of diagnoses. Altogether, our data reveal that GOAT‐levels can be used as a non‐invasive biomarker for significant PCa diagnosis in patients at risk of PCa (with PSA: 3‐20 ng/mL).
Highlights
Prostate cancer (PCa) has emerged as the most frequent cancer type among men, with an estimation of 164 690 new cases in the United States for 2018 (10% of all new cancer cases).[1]
The proportion of men with metastatic PCa at the time of diagnosis have decreased dramatically with the introduction of PSA as a screening test, more men are being diagnosed with PCa, with the majority having early stage, clinically indolent disease, the majority of which may never have led to harm.[12]
It has been proposed that treatment of indolent cancer may cause a patient more harm than good as biopsies and PCa treatments have been associated with psychological distress, loss of bodily function, pain, suffering for patients and with a decrease in the patient quality of life (QoL).[13]
Summary
Prostate cancer (PCa) has emerged as the most frequent cancer type among men, with an estimation of 164 690 new cases in the United States for 2018 (10% of all new cancer cases).[1]. Clinical management of aggressive PCa, that is metastatic and castration‐resistant PCa (CRPC), faces major limitations, including unresponsive patients and development of resistance to hormonal and chemical therapies.[5,6] there is an important unmet clinical need for the identification and validation of new, reliable and specific biomarkers for early diagnosis of PCa, as well as for prediction of disease prognosis and treatment response, etc., which would improve patient survival and QoL and would reduce substantially the number of unnecessary biopsies in patients with suspect of PCa based on PSA test
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