Tissue metabolite profiling identifies differentiating and prognostic biomarkers for prostate carcinoma
Tissue metabolite profiling identifies differentiating and prognostic biomarkers for prostate carcinoma
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DOI：
10.1002/ijc.28303
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发表时间：
2013-12-15
影响因子：
6.4
通讯作者：
Kristiansen, Glen
中科院分区：
文献类型：
--
作者：
Jung, Klaus;Reszka, Regina;Kristiansen, Glen
代谢组学研究为癌症代谢中的生化变化提供了更深入的了解，是识别新生物标记物的一种有前途的工具。我们的目的是评估前列腺癌(PCa)组织中代谢产物在前列腺癌根治术后的诊断和预后方面的潜力。在95例前列腺癌患者的前列腺癌切除标本中，用气相色谱/液-质联用法测定了氨基己二酸、脑酸、葡萄糖酸、甘油磷酸乙醇胺、2-羟基苯乙酸、异戊烯焦磷酸、麦芽糖、7-甲基鸟嘌呤和三十烷酸。这些数据与临床病理变量有关，如前列腺体积、肿瘤分期、Gleason评分、术前前列腺特异性抗原和随访中的疾病复发。除葡萄糖酸和麦芽三糖在肿瘤中的水平较低外，所有九种代谢物在恶性肿瘤样本中的浓度都高于非恶性样本。受试者操作特征分析显示，所有代谢物在恶性和非恶性组织之间具有显著的区分性，在曲线下的最大面积为0.86，而除葡萄糖酸外，代谢物水平与Gleason评分和肿瘤分期之间无相关性。单因素COX回归和Kaplan-Meier分析显示，氨基二酸、葡萄糖酸和麦芽三糖水平与生化肿瘤复发(前列腺特异性抗原0.2 ng/mL)相关。在多因素Cox回归分析中，氨基己二酸、肿瘤分期和Gleason评分仍是预测生化复发的独立标志物。这项研究证明，前列腺癌组织中的代谢物可以与传统的临床病理因素相结合，作为有前景的诊断和预后工具。
Metabolomic research offers a deeper insight into biochemical changes in cancer metabolism and is a promising tool for identifying novel biomarkers. We aimed to evaluate the diagnostic and prognostic potential of metabolites in prostate cancer (PCa) tissue after radical prostatectomy. In matched malignant and nonmalignant prostatectomy samples from 95 PCa patients, aminoadipic acid, cerebronic acid, gluconic acid, glycerophosphoethanolamine, 2-hydroxybehenic acid, isopentenyl pyrophosphate, maltotriose, 7-methylguanine and tricosanoic acid were determined within a global metabolite profiling study using gas chromatography/liquid chromatography-mass spectrometry. The data were related to clinicopathological variables like prostate volume, tumor stage, Gleason score, preoperative prostate-specific antigen and disease recurrence in the follow-up. All nine metabolites showed higher concentrations in malignant than in nonmalignant samples except for gluconic acid and maltotriose, which had lower levels in tumors. Receiver -operating characteristics analysis demonstrated a significant discrimination for all metabolites between malignant and nonmalignant tissue with a maximal area under the curve of 0.86 for tricosanoic acid, whereas no correlation was observed between the metabolite levels and the Gleason score or tumor stage except for gluconic acid. Univariate Cox regression and Kaplan-Meier analyses showed that levels of aminoadipic acid, gluconic acid and maltotriose were associated with the biochemical tumor recurrence (prostate-specific antigen > 0.2 ng/mL). In multivariate Cox regression analyses, aminoadipic acid together with tumor stage and Gleason score remained in a model as independent marker for prediction of biochemical recurrence. This study proved that metabolites in PCa tissue can be used, in combination with traditional clinicopathological factors, as promising diagnostic and prognostic tools.