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Published July 31, 2021 | Version v1
Journal article Open

In1-Ghrelin Splicing Variant as a Key Element in the Pathophysiological Association Between Obesity and Prostate Cancer

  • 1. Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain; Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain; CIBER Physiopathology of Obesity and Nutrition (CIBERobn), 14004 Cordoba, Spain
  • 2. Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain; Urology Service, HURS/IMIBIC, 14004 Cordoba, Spain
  • 3. Leuven Biostatistics and Statistical Bioinformatics Centre (L-BioStat), Katholiek Universiteit (KU) Leuven, University of Leuven, Leuven, Belgium
  • 4. Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain; CIBER Physiopathology of Obesity and Nutrition (CIBERobn), 14004 Cordoba, Spain. Lipids and Atherosclerosis Unit, Internal Medicine Unit, Reina Sofia University Hospital. 14004 Cordoba, Spain
  • 5. Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain; Urology Service, HURS/IMIBIC, 14004 Cordoba, Spain.

Description

Abstract

Context: Recent studies emphasize the importance of considering the metabolic status to develop personalized medicine approaches. This is especially relevant in prostate cancer (PCa), wherein the diagnostic capability of PSA dramatically drops when considering patients with PSA levels ranging 3-10 ng/mL, the so-called “grey-zone”. Hence, additional non-invasive diagnostic and/or prognostic PCa biomarkers are urgently needed, especially in the metabolic-status context.

Objective: To assess the potential relation of urine In1-ghrelin (a ghrelin splicing variant) levels with metabolic-related/pathological conditions (e.g. obesity/diabetes/BMI/insulin-glucose levels), and to define its potential clinical value in PCa (diagnostic/prognostic capacity) and relationship with PCa-risk in patients with PSA in the grey-zone.

Methods: Urine In1-ghrelin levels were measured by radioimmunoassay in a clinically/metabolically/pathologically well-characterized cohort of patients without (n=397) or with (n=213) PCa with PSA in the grey-zone.

Results: Key obesity-related factors associated with PCa-risk (BMI/diabetes/glucose/insulin) were strongly correlated to In1-ghrelin levels. Importantly, In1-ghrelin levels were higher in PCa patients compared to control patients (with suspect of PCa but negative-biopsy). Moreover, high In1-ghrelin levels were associated with increased PCa-risk and linked to PCa-aggressiveness (e.g. tumour-stage/lymphovascular-invasion). In1-ghrelin levels added significant diagnostic value to a clinical model consisting of age, suspicious-DRE, previous-biopsy, and PSA levels. Furthermore, a multivariate model consisting of clinical and metabolic variables, including In1-ghrelin levels, showed high specificity and sensitivity to diagnose PCa (AUC=0.740).

Conclusions: Urine In1-ghrelin levels are associated with obesity-related factors and PCa risk/aggressiveness, and could represent a novel and valuable non-invasive PCa biomarker, as well as a potential link in the pathophysiological relationship between obesity and PCa.

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In1-ghrelin splicing variant as a key element in the pathophysiological association between obesity and prostate cancer.pdf

Additional details

Funding

P2Med – IMIBIC Fellowship Programme for Personalised and Precision Medicine 847468
European Commission