Metabolomic biomarkers of pancreatic cancer: a meta-analysis study.
Metabolomic biomarkers of pancreatic cancer: a meta-analysis study.
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DOI：
10.18632/oncotarget.20324
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发表时间：
2017-09-15
期刊：
影响因子：
--
通讯作者：
Cheema AK
中科院分区：
文献类型：
--
作者：
Mehta KY;Wu HJ;Menon SS;Fallah Y;Zhong X;Rizk N;Unger K;Mapstone M;Fiandaca MS;Federoff HJ;Cheema AK
胰腺癌（PC）是一种侵袭性疾病，死亡率高，然而，没有血液检测用于早期发现和诊断这种疾病。几个研究小组已经报道了基于代谢组学的临床研究，以确定PC的生物标志物，但是缺乏可用于荟萃分析和生物标志物验证的集中代谢物生物标志物库。此外，由于PC的发病率与代谢综合征和2型糖尿病（T2DM）相关，因此需要解除这些常见的代谢失调，否则这些代谢失调可能会降低代谢组学生物特征的临床效用。在这里，我们试图在一个独立的PC受试者组中外部复制其他几个组报告的PC代谢物生物标志物。我们的研究设计包括一个用作非癌症对照的T2DM队列和一个诊断为结直肠癌（CRC）的单独队列，作为癌症疾病对照，以消除可能的癌症通用生物标志物。我们使用靶向质谱法对文献策划的代谢物标志物进行定量，并确定了一个生物标志物组，该生物标志物组可以高准确度区分正常对照（NC）和PC患者。然而，对我们的CRC模型的进一步评估显示，PC生物标志物组的特异性下降。综上所述，我们的研究强调了癌症生物标志物研究需要更稳健的研究设计，以最大限度地提高转化价值和临床实施。
Pancreatic cancer (PC) is an aggressive disease with high mortality rates, however, there is no blood test for early detection and diagnosis of this disease. Several research groups have reported on metabolomics based clinical investigations to identify biomarkers of PC, however there is a lack of a centralized metabolite biomarker repository that can be used for meta-analysis and biomarker validation. Furthermore, since the incidence of PC is associated with metabolic syndrome and Type 2 diabetes mellitus (T2DM), there is a need to uncouple these common metabolic dysregulations that may otherwise diminish the clinical utility of metabolomic biosignatures. Here, we attempted to externally replicate proposed metabolite biomarkers of PC reported by several other groups in an independent group of PC subjects. Our study design included a T2DM cohort that was used as a non-cancer control and a separate cohort diagnosed with colorectal cancer (CRC), as a cancer disease control to eliminate possible generic biomarkers of cancer. We used targeted mass spectrometry for quantitation of literature-curated metabolite markers and identified a biomarker panel that discriminates between normal controls (NC) and PC patients with high accuracy. Further evaluation of our model with CRC, however, showed a drop in specificity for the PC biomarker panel. Taken together, our study underscores the need for a more robust study design for cancer biomarker studies so as to maximize the translational value and clinical implementation.
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