Ghrelin O-acyltransferase (GOAT) enzyme is overexpressed in prostate cancer, and its levels are associated with patient's metabolic status: Potential value as a non-invasive biomarker.
Ghrelin-O-acyltransferase (GOAT) is the key enzyme regulating ghrelin activity, and has been proposed as a potential therapeutic target for obesity/diabetes and as a biomarker in some endocrine-related cancers. However, GOAT presence and putative role in prostate-cancer (PCa) is largely unknown. Here, we demonstrate, for the first time, that GOAT is overexpressed (mRNA/protein-level) in prostatic tissues (n = 52) and plasma/urine-samples (n = 85) of PCa-patients, compared with matched controls [healthy prostate tissues (n = 12) and plasma/urine-samples from BMI-matched controls (n = 28), respectively]. Interestingly, GOAT levels in PCa-patients correlated with aggressiveness and metabolic conditions (i.e. diabetes). Actually, GOAT expression was regulated by metabolic inputs (i.e. In1-ghrelin, insulin/IGF-I) in cultured normal prostate cells and PCa-cell lines. Importantly, ROC-curve analysis unveiled a valuable diagnostic potential for GOAT to discriminate PCa at the tissue/plasma/urine-level with high sensitivity/specificity, particularly in non-diabetic individuals. Moreover, we discovered that GOAT is secreted by PCa-cells, and that its levels are higher in urine samples from a stimulated post-massage vs. pre-massage prostate-test. In conclusion, plasmatic GOAT levels exhibit high specificity/sensitivity to predict PCa-presence compared with other PCa-biomarkers, especially in non-diabetic individuals, suggesting that GOAT holds potential as a novel non-invasive PCa-biomarker.
Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; CIBERobn, Córdoba, Spain; ceiA3, Córdoba, Spain.
Daniel
D
Hormaechea-Agulla
Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Urology Service, HURS, Córdoba, Spain.
Enrique
E
Gómez-Gómez
Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; CIBERobn, Córdoba, Spain; ceiA3, Córdoba, Spain.
Alejandro
A
Ibáñez-Costa
Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Urology Service, HURS, Córdoba, Spain.
Julia
J
Carrasco-Valiente
Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; CIBERobn, Córdoba, Spain; ceiA3, Córdoba, Spain.
Esther
E
Rivero-Cortés
Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; CIBERobn, Córdoba, Spain; ceiA3, Córdoba, Spain.
Fernando
F
L-López
Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; CIBERobn, Córdoba, Spain; ceiA3, Córdoba, Spain.
Sergio
S
Pedraza-Arevalo
Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Urology Service, HURS, Córdoba, Spain.
José
J
Valero-Rosa
Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Anatomical Pathology Service, HURS, Córdoba, Spain.
Rafael
R
Sánchez-Sánchez
Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Anatomical Pathology Service, HURS, Córdoba, Spain.
Rosa
R
Ortega-Salas
Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Anatomical Pathology Service, HURS, Córdoba, Spain.
María M
MM
Moreno
Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; CIBERobn, Córdoba, Spain; ceiA3, Córdoba, Spain.
Manuel D
MD
Gahete
Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; CIBERobn, Córdoba, Spain; Lipids and Atherosclerosis Unit, HURS, Córdoba, Spain.
José
J
López-Miranda
Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Urology Service, HURS, Córdoba, Spain.
María J
MJ
Requena
Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; CIBERobn, Córdoba, Spain; ceiA3, Córdoba, Spain. Electronic address: justo@uco.es.
Justo P
JP
Castaño
Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; CIBERobn, Córdoba, Spain; ceiA3, Córdoba, Spain. Electronic address: raul.luque@uco.es.
Raúl M
RM
Luque
D000217:Acyltransferases / Q000097:blood* / Q000235:genetics / Q000652:urine; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics / Q000652:urine; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D003920:Diabetes Mellitus / Q000097:blood / Q000201:enzymology; D050171:Dyslipidemias / Q000097:blood / Q000201:enzymology; D004734:Energy Metabolism; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000201:enzymology; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000201:enzymology; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000097:blood / Q000201:enzymology* / Q000235:genetics / Q000652:urine; D012333:RNA, Messenger / Q000235:genetics; D012372:ROC Curve; D015203:Reproducibility of Results; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D000217:Acyltransferases; C542776:MBOAT4 protein, human
Biomarker; Diabetes; Diagnosis; GOAT-enzyme; Ghrelin; Prostate cancer