Ex vivo metabolic fingerprinting identifies biomarkers predictive of prostate cancer recurrence following radical prostatectomy

• Published in: British journal of cancer 2017-11, Vol.117 (11), p.1656-1664
• Main Authors: Braadland, Peder R, Giskeødegård, Guro, Sandsmark, Elise, Bertilsson, Helena, Euceda, Leslie R, Hansen, Ailin F, Guldvik, Ingrid J, Selnæs, Kirsten M, Grytli, Helene H, Katz, Betina, Svindland, Aud, Bathen, Tone F, Eri, Lars M, Nygård, Ståle, Berge, Viktor, Taskén, Kristin A, Tessem, May-Britt
• Format: Article
• Language: English
• Subjects: 692/420/755; 692/53/2423; 692/699/67/589/466; 692/700/565/545; Aged; Biomarkers; Biomarkers, Tumor; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cancer surgery; Choline; Citric acid; Citric Acid - metabolism; Creatine; Drug Resistance; Epidemiology; Fingerprinting; Health risk assessment; Health risks; Humans; Magnetic Resonance Spectroscopy; Male; Metabolites; Middle Aged; Molecular Medicine; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - metabolism; Nomograms; Oncology; Proportional Hazards Models; Prostate cancer; Prostatectomy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; Retrospective Studies; Risk assessment; Risk factors; Spectroscopy; Spermine; Spermine - metabolism; Survival; Translational Therapeutics; Urological surgery
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2017.346

Background: Robust biomarkers that identify prostate cancer patients with high risk of recurrence will improve personalised cancer care. In this study, we investigated whether tissue metabolites detectable by high-resolution magic angle spinning magnetic resonance spectroscopy (HR-MAS MRS) were associated with recurrence following radical prostatectomy. Methods: We performed a retrospective ex vivo study using HR-MAS MRS on tissue samples from 110 radical prostatectomy specimens obtained from three different Norwegian cohorts collected between 2002 and 2010. At the time of analysis, 50 patients had experienced prostate cancer recurrence. Associations between metabolites, clinicopathological variables, and recurrence-free survival were evaluated using Cox proportional hazards regression modelling, Kaplan–Meier survival analyses and concordance index (C-index). Results: High intratumoural spermine and citrate concentrations were associated with longer recurrence-free survival, whereas high (total-choline+creatine)/spermine (tChoCre/Spm) and higher (total-choline+creatine)/citrate (tChoCre/Cit) ratios were associated with shorter time to recurrence. Spermine concentration and tChoCre/Spm were independently associated with recurrence in multivariate Cox proportional hazards modelling after adjusting for clinically relevant risk factors (C-index: 0.769; HR: 0.72; P =0.016 and C-index: 0.765; HR: 1.43; P =0.014, respectively). Conclusions: Spermine concentration and tChoCre/Spm ratio in prostatectomy specimens were independent prognostic markers of recurrence. These metabolites can be noninvasively measured in vivo and may thus offer predictive value to establish preoperative risk assessment nomograms.