胃癌呼气标志物—甲基庚烯酮的分子代谢机制与临床早期诊断价值的研究

项目名称： 胃癌呼气标志物—甲基庚烯酮的分子代谢机制与临床早期诊断价值的研究

项目编号： No.81472750

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘虎

作者单位： 安徽医科大学

项目金额： 72万元

中文摘要： 胃癌的早期诊断是改善其预后的关键。肿瘤的一个重要特征是代谢异常，其异常代谢产物的检测为肿瘤早期诊断提供了重要线索。本课题组前期在胃癌患者呼气中检出异常增多的挥发性有机化合物-甲基庚烯酮，分析该挥发性有机化合物可作为潜在的胃癌早期诊断的呼气标志物，并推测其为胃癌异常代谢产物，但其分子代谢机制尚不明确。基于国内外相关文献我们提出假说：胃癌细胞因氧自由基代谢异常，细胞内氧自由基增加，从而发生脂质过氧化，产生过量的丙酮和异戊二烯，两者在胃液盐酸环境下生成过量甲基庚烯酮。该产物经自由扩散透过毛细血管壁进入血液循环，最终经肺泡气体交换呼出。我们拟通过同位素示踪技术探明甲基庚烯酮的前体物质;通过质粒转染、RNAi及Western Blot技术筛选调控其生成的抗氧化酶及基因；最后通过大样本临床试验验证此假说，确立甲基庚烯酮早期诊断胃癌的参考值及灵敏度和特异度，为其早期诊断胃癌提供理论依据和循证医学证据。

中文关键词： C07_胃肿瘤；早期诊断；甲基庚烯酮；分子代谢机制；诊断价值

英文摘要： Early diagnoses of gastric cancer can significantly improve its prognoses. An important characteristic of cancer, abnormal metabolisms, may provide a new clue for early diagnoses by detection of cancer metabolites. Our research team previously found that methylheptenone, a kind of volatile organic compounds, abnormally elevated in the breath of gastric cancer patients. It can potentially diagnose gastric cancer early from exhaled breath of gastric cancer patients, which is speculated as the over-produced metabolite of gastric cancer. However, the molecular metabolic mechanisms of this breath biomarker are unclear. Based on former literatures, we drew the following hypotheses: due to the abnormal metabolisms, oxygen radicals were over produced in gastric cancer cells, which resulted in lipid peroxidation(LPO). LPO could produce more acetone that became methylheptenone in the acid environment of stomach. Methylheptenone could enter the bloodstream through capillaries and be exhaled by the lung of GC patient.We plan to explore the precursors of methylheptenone by isotope tracer technique，screen the antioxidases and related genes by plasmid transfection, RNAi and Western Blot, and finally verify the hypotheses and determine the diagnostic values of the breath biomarker by large-sample clinical trials for the purpose of clarifying its molecular metabolic mechanisms and providing the theoretical foundations and clinical evidences for early diagnoses of GC with this volatile biomarker.

英文关键词： gastric cancer;early diagnosis;methylheptenone;molecular metabolic mechanisms;diagnostic values