Quantitative global lipidomics analysis of patients with ovarian cancer versus benign adnexal mass.
Quantitative global lipidomics analysis of patients with ovarian cancer versus benign adnexal mass.
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DOI：
10.1038/s41598-021-97433-x
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发表时间：
2021-09-13
影响因子：
4.6
通讯作者：
Yan L
中科院分区：
文献类型：
--
作者：
Buas MF;Drescher CW;Urban N;Li CI;Bettcher L;Hait NC;Moysich KB;Odunsi K;Raftery D;Yan L
脂质代谢改变已成为卵巢癌（OC）的一个重要特征，但脂质代谢物的翻译潜力，以帮助诊断和分诊仍然没有得到证实。我们对附件包块患者的脂质代谢表型进行了多层次的调查，将血浆和腹水的定量脂质组学分析与公开的肿瘤转录组数据相结合。使用Sciex Lipidyzer，我们评估了两个患者队列中> 500种血浆脂质的浓度-（i）100名患有OC（50）或良性肿瘤（50）的女性的试验组，以及（ii）118名患有恶性（60）或良性（58）附件肿块的女性的独立组。在两个队列中，病例与对照相比，249种脂质种类和几种脂质类别显著减少（FDR < 0.05）。三酰甘油、磷脂酰胆碱、胆固醇酯等23种代谢产物的Bonferroni显著性检验（P < 9.16 × 10-5）。某些脂质表现出更大的变化，在早期（二酰基甘油）或晚期（溶血磷脂）的情况下，和多种脂质在血浆和腹水呈正相关。脂蛋白受体基因表达在OC与良性肿瘤中有显著差异。重要的是，几种血浆脂质种类，如DAG（16：1/18：1），提高了CA 125区分早期OC病例与良性对照的准确性，并在年龄和BMI校正的多变量模型中，在90%的灵敏度下，特异性增加了15-20%。这项研究提供了新的洞察OC和良性疾病之间的全身和局部脂质代谢差异，进一步暗示改变OC生物学中的脂质摄取，并推进血浆脂质代谢物作为OC诊断和分诊的循环生物标志物的补充类别。
Altered lipid metabolism has emerged as an important feature of ovarian cancer (OC), yet the translational potential of lipid metabolites to aid in diagnosis and triage remains unproven. We conducted a multi-level interrogation of lipid metabolic phenotypes in patients with adnexal masses, integrating quantitative lipidomics profiling of plasma and ascites with publicly-available tumor transcriptome data. Using Sciex Lipidyzer, we assessed concentrations of > 500 plasma lipids in two patient cohorts—(i) a pilot set of 100 women with OC (50) or benign tumor (50), and (ii) an independent set of 118 women with malignant (60) or benign (58) adnexal mass. 249 lipid species and several lipid classes were significantly reduced in cases versus controls in both cohorts (FDR < 0.05). 23 metabolites—triacylglycerols, phosphatidylcholines, cholesterol esters—were validated at Bonferroni significance (P < 9.16 × 10–5). Certain lipids exhibited greater alterations in early- (diacylglycerols) or late-stage (lysophospholipids) cases, and multiple lipids in plasma and ascites were positively correlated. Lipoprotein receptor gene expression differed markedly in OC versus benign tumors. Importantly, several plasma lipid species, such as DAG(16:1/18:1), improved the accuracy of CA125 in differentiating early-stage OC cases from benign controls, and conferred a 15–20% increase in specificity at 90% sensitivity in multivariate models adjusted for age and BMI. This study provides novel insight into systemic and local lipid metabolic differences between OC and benign disease, further implicating altered lipid uptake in OC biology, and advancing plasma lipid metabolites as a complementary class of circulating biomarkers for OC diagnosis and triage.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
4.3
作者：
Baenke F;Peck B;Miess H;Schulze A
通讯作者：
Schulze A
影响因子：
3.7
作者：
Palmer C;Duan X;Hawley S;Scholler N;Thorpe JD;Sahota RA;Wong MQ;Wray A;Bergan LA;Drescher CW;McIntosh MW;Brown PO;Nelson BH;Urban N
通讯作者：
Urban N
DOI：
10.1097/igc.0b013e318251c97d
发表时间：
2012-05
期刊：
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
影响因子：
--
作者：
Bast RC Jr;Skates S;Lokshin A;Moore RG
通讯作者：
Moore RG
影响因子：
4.6
作者：
Gaul DA;Mezencev R;Long TQ;Jones CM;Benigno BB;Gray A;Fernández FM;McDonald JF
通讯作者：
McDonald JF