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
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, PO Box 4953 Nydalen, Oslo 0424, Norway.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo 0313, Norway.
Br J Cancer. 2017 Nov 21;117(11):1656-1664. doi: 10.1038/bjc.2017.346. Epub 2017 Oct 3.
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.
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).
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).
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.
能够识别出复发风险高的前列腺癌患者的强大生物标志物将改善个性化癌症治疗。在本研究中，我们调查了通过高分辨率魔角旋转磁共振波谱（HR-MAS MRS）检测到的组织代谢物是否与根治性前列腺切除术后的复发相关。
我们对2002年至2010年间从挪威三个不同队列收集的110份根治性前列腺切除标本的组织样本进行了一项回顾性离体研究，采用HR-MAS MRS。在分析时，50名患者经历了前列腺癌复发。使用Cox比例风险回归模型、Kaplan-Meier生存分析和一致性指数（C指数）评估代谢物、临床病理变量和无复发生存之间的关联。
肿瘤内精胺和柠檬酸盐浓度高与无复发生存期延长相关，而高（总胆碱+肌酸）/精胺（tChoCre/Spm）和更高（总胆碱+肌酸）/柠檬酸盐（tChoCre/Cit）比值与复发时间缩短相关。在调整临床相关风险因素后，精胺浓度和tChoCre/Spm在多变量Cox比例风险模型中与复发独立相关（C指数：0.769；风险比：0.72；P=0.016和C指数：0.765；风险比：1.43；P=0.014，分别）。
前列腺切除标本中的精胺浓度和tChoCre/Spm比值是复发的独立预后标志物。这些代谢物可以在体内进行无创测量，因此可能为建立术前风险评估列线图提供预测价值。
