Jones Christina M, Monge María Eugenia, Kim Jaeyeon, Matzuk Martin M, Fernández Facundo M
School of Chemistry & Biochemistry, Georgia Institute of Technology , 901 Atlantic Drive NW, Atlanta, Georgia 30332, United States.
J Proteome Res. 2015 Feb 6;14(2):917-27. doi: 10.1021/pr5009948. Epub 2015 Jan 16.
Ovarian cancer is a deadly disease killing more than any other gynecologic cancer. Nonspecific symptoms, combined with a lack of early detection methods, contribute to late diagnosis and low five-year survival rates. High-grade serous carcinoma (HGSC) is the most common and deadliest subtype that results in 90% of ovarian cancer deaths. To investigate metabolic patterns for early detection of this deadly ovarian cancer, Dicer-Pten double knockout (DKO) mice that phenocopy many of the features of metastatic HGSC observed in women were studied. Using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), serum samples from 14 early-stage tumor (ET) DKO mice and 11 controls were analyzed in depth to screen for metabolic signatures capable of differentiating early-stage HGSC from controls. Iterative multivariate classification selected 18 metabolites that, when considered as a panel, yielded 100% accuracy, sensitivity, and specificity for classification. Altered metabolic pathways reflected in that panel included those of fatty acids, bile acids, glycerophospholipids, peptides, and some dietary phytochemicals. These alterations revealed impacts to cellular energy storage and membrane stability, as well as changes in defenses against oxidative stress, shedding new light on the metabolic alterations associated with early ovarian cancer stages.
卵巢癌是一种致命疾病，其致死率高于其他任何妇科癌症。非特异性症状加上缺乏早期检测方法，导致诊断延迟和五年生存率较低。高级别浆液性癌（HGSC）是最常见且最致命的亚型，导致90%的卵巢癌死亡。为了研究用于早期检测这种致命卵巢癌的代谢模式，对模拟女性转移性HGSC许多特征的Dicer-Pten双敲除（DKO）小鼠进行了研究。使用超高效液相色谱-质谱联用仪（UPLC-MS），对14只早期肿瘤（ET）DKO小鼠和11只对照小鼠的血清样本进行了深入分析，以筛选能够区分早期HGSC与对照的代谢特征。迭代多变量分类选择了18种代谢物，将其作为一个组合考虑时，分类的准确率、灵敏度和特异性均达到100%。该组合中反映出的代谢途径改变包括脂肪酸、胆汁酸、甘油磷脂、肽和一些膳食植物化学物质的代谢途径。这些改变揭示了对细胞能量储存和膜稳定性的影响，以及抗氧化应激防御的变化，为与卵巢癌早期阶段相关的代谢改变提供了新的线索。
