Quantitative global lipidomics analysis of patients with ovarian cancer versus benign adnexal mass

AbstractAltered 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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Abstract 1873: Plasma heat shock protein 90kDa beta member 1 levels predict both early stage and advanced stage ovarian cancer independently from cancer antigen 125 in patients with an indeterminate adnexal mass

10.1158/1538-7445.am2014-1873 ◽

2014 ◽

Author(s):

Matthew S. Block ◽

Matthew J. Maurer ◽

Krista Goergen ◽

Kimberly R. Kalli ◽

Courtney L. Erskine ◽

...

Keyword(s):

Ovarian Cancer ◽

Heat Shock ◽

Heat Shock Protein ◽

Adnexal Mass ◽

Early Stage ◽

Advanced Stage ◽

Cancer Antigen 125 ◽

Cancer Antigen

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Chemokine expression in patients with ovarian cancer or benign ovarian tumors

Archives of Medical Science ◽

10.5114/aoms/110672 ◽

2021 ◽

Author(s):

Marek Nowak ◽

Łukasz Janas ◽

Malwina Soja ◽

Ewa Głowacka ◽

Krzysztof Szyłło ◽

...

Keyword(s):

Ovarian Cancer ◽

Adnexal Mass ◽

Advanced Ovarian Cancer ◽

Serum Levels ◽

Ovarian Tumors ◽

Benign Tumors ◽

Significant Elevation ◽

Chemiluminescence Method ◽

Benign Ovarian Tumors ◽

Potential Use

IntroductionChemokines play a crucial role in tumor growth and progression according to proangiogenic and immunosuppressive acting. This study was aimed to investigate the serum levels of selected chemokines in patients with ovarian cancer or benign ovarian tumors to point on their role in tumorigenesis and their potential use in preoperative diagnosing of adnexal mass.Material and methodsThe study group consisted of 59 women with ovarian cancer: 17 epithelial ovarian cancer (EOC) patients and 42 women with benign ovarian tumors. We measured in sera obtained preoperatively the level of CA125 and the panel of 5 chemokines: CX3CL1/Fractalkine, CXCL1/GRO-α, CXCL12/SDF-1, CCL20/MIP-3α and IL-17F, using chemiluminescence method with multiplexed bead based immunoassay.ResultsCX3CL1 was significantly elevated in sera of advanced ovarian cancer patients compared to women with benign ovarian tumors. The significant elevation of CXCL1 was also observed (both: early and advanced stage). The similar pattern was present with standard ovarian cancer marker – CA125. In our patients with endometriotic cysts CA125 levels were significantly higher than in women with other benign tumors whereas all analyzed chemokines had similar serum titers in patients with endometriotic vs other benign ovarian cysts.ConclusionsCX3CL1 and CXCL1 are elevated in sera of EOC patients what points on their role in cancer development. Moreover, they might be useful in preoperative differential diagnosis of ovarian tumors, especially as they were not elevated in cases of endometriosis.

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The plasma lipidome of the Quaker parrot (Myiopsitta monachus)

PLoS ONE ◽

10.1371/journal.pone.0240449 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0240449

Author(s):

Hugues Beaufrère ◽

Sara M. Gardhouse ◽

R. Darren Wood ◽

Ken D. Stark

Keyword(s):

Plasma Lipids ◽

Plasma Lipid ◽

Principal Component ◽

Blood Lipid ◽

Myiopsitta Monachus ◽

Structure Database ◽

Lipid Species ◽

Health And Disease ◽

The Impact ◽

Fatty Acyls

Dyslipidemias and lipid-accumulation disorders are common in captive parrots, in particular in Quaker parrots. Currently available diagnostic tests only measure a fraction of blood lipids and have overall problematic cross-species applicability. Comprehensively analyzing lipids in the plasma of parrots is the first step to better understand their lipid metabolism in health and disease, as well as to explore new lipid biomarkers. The plasma lipidome of 12 Quaker parrots was investigated using UHPLC-MS/MS with both targeted and untargeted methods. Targeted methods on 6 replicates measured 432 lipids comprised of sterol, cholesterol ester, bile acid, fatty acid, acylcarnitine, glycerolipid, glycerophospholipid, and sphingolipid panels. For untargeted lipidomics, precursor ion mass-to-charge ratios were matched to corresponding lipids using the LIPIDMAPS structure database and LipidBlast at the sum composition or acyl species level of information. Sterol lipids and glycerophospholipids constituted the majority of plasma lipids on a molar basis. The most common lipids detected with the targeted methods included free cholesterol, CE(18:2), CE(20:4) for sterol lipids; PC(36:2), PC(34:2), PC(34:1) for glycerophospholipids; TG(52:3), TG(54:4), TG(54:5), TG(52:2) for glycerolipids; SM(d18:1/16:0) for sphingolipids; and palmitic acid for fatty acyls. Over a thousand different lipid species were detected by untargeted lipidomics. Sex differences in the plasma lipidome were observed using heatmaps, principal component analysis, and discriminant analysis. This report presents the first comprehensive database of plasma lipid species in psittacine birds and paves the way for further research into blood lipid diagnostics and the impact of diet, diseases, and drugs on the parrot plasma lipidome.

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Expression of glucose-regulated protein 78 (GRP78) and its regulator microrna-181 during the development and progression of ovarian cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.5579 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 5579-5579

Author(s):

Animesh Barua ◽

Aparna Yellapa ◽

Salvatore A Grasso ◽

Jacques S Abramowicz ◽

Sameer Sharma ◽

...

Keyword(s):

Ovarian Cancer ◽

Late Stage ◽

Malignant Tumors ◽

Early Stage ◽

Distinct Pattern ◽

Ovarian Tumors ◽

Serous Carcinoma ◽

Surface Epithelium ◽

Benign Tumors ◽

Potential Marker

5579 Background: Ovarian cancer (OVCA) is a lethal malignancy of women with a distinct pattern of metastasis through peritoneal dissemination. Sustained exposure of the ovaries to oxidative stress due to inflammatory processes including ovulatory genotoxicity, makes the ovarian microenvironment conducive to malignant cell proliferation. GRP78 is a stress-inducible protein which resides in the endoplasmic reticulum of the cell. Thus GRP78 may be a marker of ovarian tumor associated stress and could represent a therapeutic target for OVCA. The goal of this study was to examine if GRP78 expression increases in association with OVCA development and determine the molecular mechanism of its increase in ovarian tumors. Methods: All tissues were collected from patients who underwent surgery and processed for immunohistochemistry (IHC), proteomic study (2D-WB) and miRNA expression. Expression of GRP78 was examined in paraffin sections of normal ovaries (n = 20), benign (serous cystadenoma, n = 15 and cystadenofibroma, n = 5) and ovaries with papillary serous carcinoma at early stage (n= 20 at stages I and II) and late stage (n = 20, stages III and IV) by IHC and confirmed by 2D-WB (representative samples). Changes in miRNA-181 (post-translation regulator of GRP78) expression were examined by qRT-PCR. Results: GRP78 expression by normal ovarian surface epithelium and epithelium of benign tumors was very weak. In contrast, the intensity of GRP78 expression was significantly (p<0.05) high in early stage OVCA and increased further in late stage OVCA. An immunoreactive band of 78kDa detected by 2D-WB confirmed IHC observations. In contrast, expression of miRNA-181 by malignant tumors significantly (p<0.05) decreased as the tumor progressed to late stages. Conclusions: The results of the present study suggest that GRP78 expression is associated with the development and progression of malignant ovarian tumors. Increase in GRP78 expression was associated with the down-regulation of miRNA-181. Expression of GRP78 by malignant ovarian epithelium represents a potential marker with usefulness for targeted drug delivery. Support: Elmer and Sylvia Sramek Foundation.

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Three Biomarkers Identified From Serum Proteomic Analysis for the Detection of Early Stage Ovarian Cancer

Yearbook of Pathology and Laboratory Medicine ◽

10.1016/s1077-9108(08)70087-2 ◽

2006 ◽

Vol 2006 ◽

pp. 117-118

Author(s):

A.V. Parwani

Keyword(s):

Ovarian Cancer ◽

Proteomic Analysis ◽

Early Stage ◽

Early Stage Ovarian Cancer

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Screening for Familial Ovarian Cancer: Failure of Current Protocols to Detect Ovarian Cancer at an Early Stage According to the International Federation of Gynecology and Obstetrics System

Yearbook of Obstetrics Gynecology and Women s Health ◽

10.1016/s1090-798x(08)70568-x ◽

2006 ◽

Vol 2006 ◽

pp. 405-406

Author(s):

D.S. Miller

Keyword(s):

Ovarian Cancer ◽

Early Stage ◽

International Federation ◽

Gynecology And Obstetrics ◽

Familial Ovarian Cancer

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Cardioprotective Effects of Diet with Different Grains on Lipid Profiles and Antioxidative System in Obesity-Induced Rats

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000097 ◽

2012 ◽

Vol 82 (2) ◽

pp. 85-93 ◽

Cited By ~ 9

Author(s):

Y. Kim ◽

H. Shin ◽

S. Lee

Keyword(s):

Aortic Wall ◽

Plasma Lipids ◽

Antioxidant Activities ◽

Plasma Lipid ◽

Density Lipoprotein ◽

Thiobarbituric Acid ◽

Lipid Profiles ◽

Dietary Lipids ◽

Male Rats

In the present study, the nutritional quality of four grains including adlay (AD), buckwheat (BW), glutinous barley (GB), and white rice (WR) were evaluated in terms of plasma lipid parameters, gut transit time, and thickness of the aortic wall in rats. The rats were then raised for 4 weeks on the high-fat diet based on the American Institute of Nutrition-93 (AIN-93 G) diets containing 1 % cholesterol and 20 % dietary lipids. Forty male rats were divided into 4 groups and raised for 4 weeks with a diet containing one of the following grains: WR, AD, BW, or WB. The level of thiobarbituric acid-reactive substances (TBARS) in liver was shown to be higher in rats by the order of those fed WR, AD, GB, and BW. This indicates that other grains decreased oxidative stress in vivo more than WR. The superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase levels in the AD, BW, and GB groups were significantly higher than those in the WR group (p < 0.05). Plasma lipid profiles differed significantly according to grain combination, and decreased aortic wall thickness was consistent with the finding of decreased plasma low-density lipoprotein cholesterol (LDL-C) (p < 0.05) and increased high-density lipoprotein (HDL-C) in rats fed AD, BW, and GB (p < 0.001). The antioxidant and hypolipidemic capacities of grains are quite high, especially those of adlay, buckwheat, and glutinous barley. In conclusion, this study has demonstrated that the whole grains had a cardioprotective effect. This effect was related to several mechanisms that corresponded to lowering plasma lipids, decreasing TBARS, and increasing antioxidant activities.

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