Remodeling of central metabolism in invasive breast cancer compared to normal breast tissue - a GC-TOFMS based metabolomics study.
Remodeling of central metabolism in invasive breast cancer compared to normal breast tissue - a GC-TOFMS based metabolomics study.
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DOI：
10.1186/1471-2164-13-334
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发表时间：
2012-07-23
期刊：
影响因子：
4.4
通讯作者：
Fiehn O
中科院分区：
文献类型：
--
作者：
Budczies J;Denkert C;Müller BM;Brockmöller SF;Klauschen F;Györffy B;Dietel M;Richter-Ehrenstein C;Marten U;Salek RM;Griffin JL;Hilvo M;Orešič M;Wohlgemuth G;Fiehn O
细胞能量代谢的变化在许多类型的肿瘤中很常见，被认为是癌症的标志。气相色谱-飞行时间质谱仪(GC-TOFMS)是一种非常适合于研究中心代谢途径中的小分子的技术。然而，到目前为止，还没有在大量的乳腺癌样本中研究浸润性癌和正常乳腺组织之间的代谢变化。对271例乳腺癌和98例正常组织进行了基于GC-TOFMS的代谢组学研究。总共可以检测到468个代谢物峰；其中368个(79%)在癌组织和正常组织之间发生了显着变化(p<；0.05在训练和验证集合中)。此外，13个肿瘤标记物和7个正常组织标记物被鉴定出来，以80%的敏感度和特异度区分癌和正常组织。两种代谢物分类器以肿瘤和正常组织标记物的比率构建，以高灵敏度和特异度区分癌症和正常组织。具体来说，胞苷-5-单磷酸/十五酸代谢率是区分癌症和正常组织的最显著的指标，检测癌症的敏感度和特异度分别为94.8%和93.9%。首次通过对大量乳腺癌和正常组织的GC-TOF分析，构建了乳腺癌的全面代谢图。此外，我们的结果表明，基于光谱的方法有可能有助于对活检或临床组织样本的分析，以补充组织病理学。
Changes in energy metabolism of the cells are common to many kinds of tumors and are considered a hallmark of cancer. Gas chromatography followed by time-of-flight mass spectrometry (GC-TOFMS) is a well-suited technique to investigate the small molecules in the central metabolic pathways. However, the metabolic changes between invasive carcinoma and normal breast tissues were not investigated in a large cohort of breast cancer samples so far. A cohort of 271 breast cancer and 98 normal tissue samples was investigated using GC-TOFMS-based metabolomics. A total number of 468 metabolite peaks could be detected; out of these 368 (79%) were significantly changed between cancer and normal tissues (p<0.05 in training and validation set). Furthermore, 13 tumor and 7 normal tissue markers were identified that separated cancer from normal tissues with a sensitivity and a specificity of >80%. Two-metabolite classifiers, constructed as ratios of the tumor and normal tissues markers, separated cancer from normal tissues with high sensitivity and specificity. Specifically, the cytidine-5-monophosphate / pentadecanoic acid metabolic ratio was the most significant discriminator between cancer and normal tissues and allowed detection of cancer with a sensitivity of 94.8% and a specificity of 93.9%. For the first time, a comprehensive metabolic map of breast cancer was constructed by GC-TOF analysis of a large cohort of breast cancer and normal tissues. Furthermore, our results demonstrate that spectrometry-based approaches have the potential to contribute to the analysis of biopsies or clinical tissue samples complementary to histopathology.
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DOI：
10.1186/bcr2572
发表时间：
2010
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Alvarez RH
通讯作者：
Alvarez RH
影响因子：
14.9
作者：
Kanehisa M;Goto S;Sato Y;Furumichi M;Tanabe M
通讯作者：
Tanabe M
影响因子：
11.2
作者：
Dang CV
通讯作者：
Dang CV
影响因子：
37.3
作者：
Denkert C;Budczies J;Weichert W;Wohlgemuth G;Scholz M;Kind T;Niesporek S;Noske A;Buckendahl A;Dietel M;Fiehn O
通讯作者：
Fiehn O
影响因子：
168.9
作者：
Michiels, S;Koscielny, S;Hill, C
通讯作者：
Hill, C