Mass-Spectrometry Analysis of Mixed-Breath, Isolated-Bronchial-Breath, and Gastric-Endoluminal-Air Volatile Fatty Acids in Esophagogastric Cancer
Mass-Spectrometry Analysis of Mixed-Breath, Isolated-Bronchial-Breath, and Gastric-Endoluminal-Air Volatile Fatty Acids in Esophagogastric Cancer
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DOI：
10.1021/acs.analchem.9b00148
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发表时间：
2019-03-05
影响因子：
7.4
通讯作者：
Hanna, George B.
中科院分区：
文献类型：
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作者：
Adam, Mina E.;Fehervari, Matyas;Hanna, George B.
非侵入性呼吸测试有可能通过促进早期检测来提高食管胃癌的生存率。本研究旨在通过分析未分化组织上方的离体顶空和定义的解剖隔室内的体内分析（包括混合呼吸、孤立支气管呼吸和胃腔内空气分析），研究食管胃癌中目标挥发性脂肪酸（VFA）的产生。通过PTR-ToF-MS和GC-MS测量VFA。在离体实验中，与来自上消化道形态正常和良性状况的对照受试者的样品中的水平相比，食管胃癌上方的顶部空间中的VFA（乙酸、丁酸、戊酸和己酸）和丙酮的水平升高。在25名食管胃癌患者和20名对照受试者中，对体内胃腔内空气中的癌症特异性VFA丁酸（P < 0.001）和戊四烯酸（P = 0.005）进行的受试者操作特征分析得出曲线下面积为0.80（95%置信区间为0.65至0.93，P = 0.01）。与混合和支气管呼吸样本相比，所有检查的VFA在食管胃腔内空气中的浓度最高。此外，与对照组相比，来自癌症患者的所有样本中的VFA均较高。癌症患者的混合呼吸和支气管呼吸中VFA水平的等效性表明，呼吸中VFA的来源主要来自肺，并且通过推断，来自体循环，而不是直接来自上消化道。这些发现强调了利用VFA进行腔内气体活检和无创混合呼出气检测食管胃癌的潜力。
A noninvasive breath test has the potential to improve survival from esophagogastric cancer by facilitating earlier detection. This study aimed to investigate the production of target volatile fatty acids (VFAs) in esophagogastric cancer through analysis of the ex vivo headspace above underivatized tissues and in vivo analysis within defined anatomical compartments, including analysis of mixed breath, isolated bronchial breath, and gastric-endoluminal air. VFAs were measured by PTR-ToF-MS and GC-MS. Levels of VFAs (acetic, butyric, pentanoic, and hexanoic acids) and acetone were elevated in ex vivo experiments in the headspace above esophagogastric cancer compared with the levels in samples from control subjects with morphologically normal and benign conditions of the upper gastrointestinal tract. In 25 patients with esophagogastric cancer and 20 control subjects, receiver-operating-characteristic analysis for the cancer-specific VFAs butyric acid (P < 0.001) and pentatonic acid (P = 0.005) within in vivo gastric-endoluminal air gave an area under the curve of 0.80 (95% confidence interval of 0.65 to 0.93, P = 0.01). Compared with mixed- and bronchial-breath samples, all examined VFAs were found in highest concentrations within esophagogastric-endoluminal air. In addition, VFAs were higher in all samples derived from cancer patients compared with in the controls. Equivalence of VFA levels within the mixed and bronchial breath of cancer patients suggests that their origin within breath is principally derived from the lungs and, by inference, from the systemic circulation as opposed to direct passage from the upper gastrointestinal tract. These findings highlight the potential to utilize VFAs for endoluminal-gas biopsies and noninvasive mixed-exhaled-breath testing for esophagogastric-cancer detection.