Diagnosis of prostate cancer by desorption electrospray ionization mass spectrometric imaging of small metabolites and lipids
Diagnosis of prostate cancer by desorption electrospray ionization mass spectrometric imaging of small metabolites and lipids
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DOI：
10.1073/pnas.1700677114
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发表时间：
2017-03-28
影响因子：
11.1
通讯作者：
Sonn, Geoffrey A.
中科院分区：
文献类型：
--
作者：
Banerjee, Shibdas;Zare, Richard N.;Sonn, Geoffrey A.
在手术时准确识别冷冻切片中的前列腺癌可能具有挑战性，限制了外科医生在前列腺切除术期间最佳确定切除边缘的能力。我们进行解吸电喷雾电离质谱成像（MSI）54个库存的人类癌和正常前列腺组织标本，调查各种各样的小代谢物，碳水化合物和脂质的空间分布。与之前的几项研究相比，我们的方法包括克雷布斯循环中间体（m/z < 200），我们发现其在区分癌症与良性组织方面具有高度的信息性。与良性前列腺细胞相比，恶性前列腺细胞表现出明显的代谢紊乱。使用“最小绝对收缩和选择算子”（Lasso），我们分析了来自EST-MS数据的所有代谢物，并确定了用于区分癌症和正常组织的代谢谱的简约集。在一组独立的样本中，我们可以使用这些模型将前列腺癌从良性标本中分类出来，每个患者的准确率接近90%。基于先前在前列腺癌中显示葡萄糖水平高而柠檬酸盐水平低的工作，我们发现当葡萄糖/柠檬酸盐离子信号比率超过1.0时，测量该比率准确地预测癌症，并且当该比率小于0.5时，测量正常前列腺。在简单的组织制备后，可以在1分钟或更短的时间内记录组织样本上的葡萄糖/柠檬酸盐比率，这与冷冻组织标本的组织病理学检查所需的20分钟或更长时间形成鲜明对比。
Accurate identification of prostate cancer in frozen sections at the time of surgery can be challenging, limiting the surgeon's ability to best determine resection margins during prostatectomy. We performed desorption electrospray ionization mass spectrometry imaging (DESI-MSI) on 54 banked human cancerous and normal prostate tissue specimens to investigate the spatial distribution of a wide variety of small metabolites, carbohydrates, and lipids. In contrast to several previous studies, our method included Krebs cycle intermediates (m/z < 200), which we found to be highly informative in distinguishing cancer from benign tissue. Malignant prostate cells showed marked metabolic derangements compared with their benign counterparts. Using the "Least absolute shrinkage and selection operator" (Lasso), we analyzed all metabolites from the DESI-MS data and identified parsimonious sets of metabolic profiles for distinguishing between cancer and normal tissue. In an independent set of samples, we could use these models to classify prostate cancer from benign specimens with nearly 90% accuracy per patient. Based on previous work in prostate cancer showing that glucose levels are high while citrate is low, we found that measurement of the glucose/citrate ion signal ratio accurately predicted cancer when this ratio exceeds 1.0 and normal prostate when the ratio is less than 0.5. After brief tissue preparation, the glucose/citrate ratio can be recorded on a tissue sample in 1min or less, which is in sharp contrast to the 20min or more required by histopathological examination of frozen tissue specimens.