Turkoglu Onur, Zeb Amna, Graham Stewart, Szyperski Thomas, Szender J Brian, Odunsi Kunle, Bahado-Singh Ray
Department of Obstetrics and Gynecology, Beaumont Hospital, 3601 W. 13 Mile Rd., Royal Oak, MI 48073, USA.
Department of Chemistry, College of Arts and Sciences, University at Buffalo, Buffalo, NY, USA.
Metabolomics. 2016 Apr;12(4). doi: 10.1007/s11306-016-0990-0. Epub 2016 Mar 8.
Metabolomics is the emerging member of "omics" sciences advancing the understanding, diagnosis and treatment of many cancers, including ovarian cancer (OC).
To systematically identify the metabolomic abnormalities in OC detection, and the dominant metabolic pathways associated with the observed alterations.
An electronic literature search was performed, up to and including January 15th 2016, for studies evaluating the metabolomic profile of patients with OC compared to controls. QUADOMICS tool was used to assess the quality of the twenty-three studies included in this systematic review.
Biological samples utilized for metabolomic analysis include: serum/plasma (n = 13), urine (n = 4), cyst fluid (n = 3), tissue (n = 2) and ascitic fluid (n = 1). Metabolites related to cellular respiration, carbohydrate, lipid, protein and nucleotide metabolism were significantly altered in OC. Increased levels of tricarboxylic acid cycle intermediates and altered metabolites of the glycolytic pathway pointed to perturbations in cellular respiration. Alterations in lipid metabolism included enhanced fatty acid oxidation, abnormal levels of glycerolipids, sphingolipids and free fatty acids with common elevations of palmitate, oleate, and myristate. Increased levels of glutamine, glycine, cysteine and threonine were commonly reported while enhanced degradations of tryptophan, histidine and phenylalanine were found. N-acetylaspartate, a brain amino acid, was found elevated in primary and metastatic OC tissue and ovarian cyst fluid. Further, elevated levels of ketone bodies including 3-hydroxybutyrate were commonly reported. Increased levels of nucleotide metabolites and tocopherols were consistent through out the studies.
Metabolomics presents significant new opportunities for diagnostic biomarker development, elucidating previously unknown mechanisms of OC pathogenesis.
代谢组学是“组学”科学中的新兴成员，推动了包括卵巢癌（OC）在内的多种癌症的理解、诊断和治疗。
系统识别卵巢癌检测中的代谢组学异常，以及与观察到的改变相关的主要代谢途径。
进行了一项电子文献检索，截至2016年1月15日，包括评估卵巢癌患者与对照组代谢组学特征的研究。使用QUADOMICS工具评估本系统评价中纳入的23项研究的质量。
用于代谢组学分析的生物样本包括：血清/血浆（n = 13）、尿液（n = 4）、囊液（n = 3）、组织（n = 2）和腹水（n = 1）。与细胞呼吸、碳水化合物、脂质、蛋白质和核苷酸代谢相关的代谢物在卵巢癌中发生了显著改变。三羧酸循环中间体水平升高和糖酵解途径代谢物改变表明细胞呼吸受到干扰。脂质代谢的改变包括脂肪酸氧化增强、甘油脂质、鞘脂和游离脂肪酸水平异常，棕榈酸、油酸和肉豆蔻酸普遍升高。普遍报道谷氨酰胺、甘氨酸、半胱氨酸和苏氨酸水平升高，同时发现色氨酸、组氨酸和苯丙氨酸降解增强。N-乙酰天门冬氨酸，一种脑氨基酸，在原发性和转移性卵巢癌组织及卵巢囊液中升高。此外，普遍报道包括3-羟基丁酸在内的酮体水平升高。核苷酸代谢物和生育酚水平升高在各项研究中是一致的。
代谢组学为诊断生物标志物开发提供了重大新机遇，阐明了卵巢癌发病机制中以前未知的机制。
