Summary of Study ST002521

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001623. The data can be accessed directly via it's Project DOI: 10.21228/M8X42D This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002521
Study TitleWide-Coverage Serum Metabolomic Profiling Reveals a Comprehensive Lipidome Signature of Ovarian Cancer.
Study SummaryDistinguishing ovarian cancer (OC) from other benign or cancerous gynecological malignancies remains a critical unmet medical need with significant implications on patient survival. Substantially better results are observed when women with OC are correctly diagnosed and ensured the right treatment. However, non-specific symptoms along with our lack of understanding of OC pathogenesis hinder its diagnosis, consequently leading to a very low survival rate. Accumulating evidence suggests the link between OC and deregulated lipid metabolism. Most studies, however, are limited by small sample sizes and metabolite coverage, thereby constraining the robustness of the results. Here, we performed a comprehensive serum lipidome profiling of OC and various other gynecological malignancies (non-OC). A relatively large patient cohort with 208 OC and 137 non-OC patients, including 93 OC patients with early-stage OC, was recruited from two independent clinical sites in South Korea. Samples were analyzed with high-coverage liquid chromatography high-resolution mass spectrometry, providing extensive lipidome coverage with 994 successfully annotated lipid features. Lipidome differences between OC and other gynecological malignancies were investigated via statistical and machine learning approaches. Our data suggest that lipidome alterations unique to OC can be detected as early as when the cancer is localized, and those changes amplify as the diseases progresses. Comparison of the relative lipid abundances revealed specific patterns based on lipid class with most lipid classes showing decreased abundance in ovarian cancer. This study provides a systemic analysis of lipidome alterations in OC, emphasizing the potential of circulating lipids as a complementary class of blood-based biomarkers for OC diagnosis.
Institute
Georgia Institute of Technology
Last NameSah
First NameSamyukta
Address901 Atlantic Dr NW, Atlanta, GA 30318
Emailssah9@gatech.edu
Phone574-678-0124
Submit Date2023-03-10
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2023-04-12
Release Version1
Samyukta Sah Samyukta Sah
https://dx.doi.org/10.21228/M8X42D
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001623
Project DOI:doi: 10.21228/M8X42D
Project Title:Wide-Coverage Serum Metabolomic Profiling Reveals a Comprehensive Lipidome Signature of Ovarian Cancer.
Project Summary:Distinguishing ovarian cancer (OC) from other benign or cancerous gynecological malignancies remains a critical unmet medical need with significant implications on patient survival. Substantially better results are observed when women with OC are correctly diagnosed and ensured the right treatment. However, non-specific symptoms along with our lack of understanding of OC pathogenesis hinder its diagnosis, consequently leading to a very low survival rate. Accumulating evidence suggests the link between OC and deregulated lipid metabolism. Most studies, however, are limited by small sample sizes and metabolite coverage, thereby constraining the robustness of the results. Here, we performed a comprehensive serum lipidome profiling of OC and various other gynecological malignancies (non-OC). A relatively large patient cohort with 208 OC and 137 non-OC patients, including 93 OC patients with early-stage OC, was recruited from two independent clinical sites in South Korea. Samples were analyzed with high-coverage liquid chromatography high-resolution mass spectrometry, providing extensive lipidome coverage with 994 successfully annotated lipid features. Lipidome differences between OC and other gynecological malignancies were investigated via statistical and machine learning approaches. Our data suggest that lipidome alterations unique to OC can be detected as early as when the cancer is localized, and those changes amplify as the diseases progresses. Comparison of the relative lipid abundances revealed specific patterns based on lipid class with most lipid classes showing decreased abundance in ovarian cancer. This study provides a systemic analysis of lipidome alterations in OC, emphasizing the potential of circulating lipids as a complementary class of blood-based biomarkers for OC diagnosis.
Institute:Georgia Institute of Technology
Last Name:Sah
First Name:Samyukta
Address:901 Atlantic Dr NW, Atlanta, GA 30318
Email:ssah9@gatech.edu
Phone:574-678-0124

Subject:

Subject ID:SU002621
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Species Group:Mammals

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Treatment
SA254051BOT42Benign Ovarian Tumor
SA254052BOT41Benign Ovarian Tumor
SA254053BOT43Benign Ovarian Tumor
SA254054BOT44Benign Ovarian Tumor
SA254055BOT40Benign Ovarian Tumor
SA254056BOT45Benign Ovarian Tumor
SA254057BOT37Benign Ovarian Tumor
SA254058BOT35Benign Ovarian Tumor
SA254059BOT34Benign Ovarian Tumor
SA254060BOT36Benign Ovarian Tumor
SA254061BOT46Benign Ovarian Tumor
SA254062BOT38Benign Ovarian Tumor
SA254063BOT39Benign Ovarian Tumor
SA254064BOT49Benign Ovarian Tumor
SA254065BOT57Benign Ovarian Tumor
SA254066BOT56Benign Ovarian Tumor
SA254067BOT58Benign Ovarian Tumor
SA254068BOT59Benign Ovarian Tumor
SA254069BOT1Benign Ovarian Tumor
SA254070BOT55Benign Ovarian Tumor
SA254071BOT54Benign Ovarian Tumor
SA254072BOT33Benign Ovarian Tumor
SA254073BOT48Benign Ovarian Tumor
SA254074BOT50Benign Ovarian Tumor
SA254075BOT51Benign Ovarian Tumor
SA254076BOT52Benign Ovarian Tumor
SA254077BOT47Benign Ovarian Tumor
SA254078BOT53Benign Ovarian Tumor
SA254079BOT11Benign Ovarian Tumor
SA254080BOT10Benign Ovarian Tumor
SA254081BOT12Benign Ovarian Tumor
SA254082BOT13Benign Ovarian Tumor
SA254083BOT15Benign Ovarian Tumor
SA254084BOT14Benign Ovarian Tumor
SA254085BOT9Benign Ovarian Tumor
SA254086BOT7Benign Ovarian Tumor
SA254087BOT2Benign Ovarian Tumor
SA254088BOT32Benign Ovarian Tumor
SA254089BOT3Benign Ovarian Tumor
SA254090BOT4Benign Ovarian Tumor
SA254091BOT6Benign Ovarian Tumor
SA254092BOT5Benign Ovarian Tumor
SA254093BOT16Benign Ovarian Tumor
SA254094BOT8Benign Ovarian Tumor
SA254095BOT28Benign Ovarian Tumor
SA254096BOT26Benign Ovarian Tumor
SA254097BOT25Benign Ovarian Tumor
SA254098BOT29Benign Ovarian Tumor
SA254099BOT30Benign Ovarian Tumor
SA254100BOT31Benign Ovarian Tumor
SA254101BOT17Benign Ovarian Tumor
SA254102BOT24Benign Ovarian Tumor
SA254103BOT27Benign Ovarian Tumor
SA254104BOT20Benign Ovarian Tumor
SA254105BOT19Benign Ovarian Tumor
SA254106BOT18Benign Ovarian Tumor
SA254107BOT21Benign Ovarian Tumor
SA254108BOT23Benign Ovarian Tumor
SA254109BOT22Benign Ovarian Tumor
SA254443BUT10benign uterine tumor
SA254444BUT9benign uterine tumor
SA254445BUT14benign uterine tumor
SA254446BUT12benign uterine tumor
SA254447BUT8benign uterine tumor
SA254448BUT13benign uterine tumor
SA254449BUT11benign uterine tumor
SA254450BUT4benign uterine tumor
SA254451BUT1benign uterine tumor
SA254452BUT15benign uterine tumor
SA254453BUT2benign uterine tumor
SA254454BUT3benign uterine tumor
SA254455BUT6benign uterine tumor
SA254456BUT5benign uterine tumor
SA254457BUT7benign uterine tumor
SA254458BUT31benign uterine tumor
SA254459BUT26benign uterine tumor
SA254460BUT25benign uterine tumor
SA254461BUT27benign uterine tumor
SA254462BUT28benign uterine tumor
SA254463BUT30benign uterine tumor
SA254464BUT29benign uterine tumor
SA254465BUT24benign uterine tumor
SA254466BUT23benign uterine tumor
SA254467BUT18benign uterine tumor
SA254468BUT17benign uterine tumor
SA254469BUT19benign uterine tumor
SA254470BUT20benign uterine tumor
SA254471BUT22benign uterine tumor
SA254472BUT21benign uterine tumor
SA254473BUT16benign uterine tumor
SA254048B2BRACA positive
SA254049B3BRACA positive
SA254050B1BRACA positive
SA254110CC32Cervical cancer
SA254111CC30Cervical cancer
SA254112CC31Cervical cancer
SA254113CC29Cervical cancer
SA254114CC35Cervical cancer
SA254115CC28Cervical cancer
SA254116CC37Cervical cancer
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Collection:

Collection ID:CO002614
Collection Summary:Serum samples were collected from two independent tissue banks in South Korea, Dongsan Hospital Human Tissue Bank and Gangnam Severance Hospital Gene Bank. The Severance cohort included 185 samples from ovarian cancer patients, 47 from women with benign ovarian tumor, 50 from invasive cervical cancer and 21 samples from patients with benign uterine tumor. Blood was collected from all patients during surgery after anesthesia and at least 8 hours of fasting. In the Dongsan cohort 88 women had ovarian cancer, 12 had benign ovarian tumor, 10 had benign uterine tumor, and 9 women had cervical cancer. As with the Severance cohort, samples from these patients were collected during surgery after anesthesia and at least 6 hours of fasting. All recruited participants were of Korean descent. Samples from both cohorts were grouped together and patients with ovarian cancer (OC) and all other gynecological malignancies (non-OC) were age matched. The matched cohort included 208 patients with ovarian cancer (mean age 51.9 years) and 137 non-OC patients (mean age 49.9 years). Disease stages and histological characteristics are given in Table 1. Among the OC patients, 93 patients had early stage (I and II) cancer. Ten of the OC patients had recurrent cancer and 9 patients have had their samples collected more than once. In addition to diseased patients, samples from normal controls (women with no known gynecological malignancies) were collected during regular health exams at Severance hospital. In this case, blood was collected at least 8 hours after fasting.
Sample Type:Blood (serum)

Treatment:

Treatment ID:TR002633
Treatment Summary:Serum samples were collected from two independent tissue banks in South Korea, Dongsan Hospital Human Tissue Bank and Gangnam Severance Hospital Gene Bank. The Severance cohort included 185 samples from ovarian cancer patients, 47 from women with benign ovarian tumor, 50 from invasive cervical cancer and 21 samples from patients with benign uterine tumor. Blood was collected from all patients during surgery after anesthesia and at least 8 hours of fasting. In the Dongsan cohort 88 women had ovarian cancer, 12 had benign ovarian tumor, 10 had benign uterine tumor, and 9 women had cervical cancer. As with the Severance cohort, samples from these patients were collected during surgery after anesthesia and at least 6 hours of fasting. All recruited participants were of Korean descent. Samples from both cohorts were grouped together and patients with ovarian cancer (OC) and all other gynecological malignancies (non-OC) were age matched. The matched cohort included 208 patients with ovarian cancer (mean age 51.9 years) and 137 non-OC patients (mean age 49.9 years). Among the OC patients, 93 patients had early stage (I and II) cancer. Ten of the OC patients had recurrent cancer and 9 patients have had their samples collected more than once. In addition to diseased patients, samples from normal controls (women with no known gynecological malignancies) were collected during regular health exams at Severance hospital. In this case, blood was collected at least 8 hours after fasting. As noted earlier, blood from diseased patients was collected after the initiation of anesthesia, and thus could not be directly compared with normal controls without introducing major confounding effects. Therefore, control samples were excluded from our main analysis. However, for information purposes only, we also provide a lipidome comparison between healthy controls and OC patients in supplemental information.

Sample Preparation:

Sampleprep ID:SP002627
Sampleprep Summary:Serum samples were thawed on ice, followed by metabolite extraction of the non-polar (lipids) metabolome. Extraction solvent was prepared by adding 725 μL of the isotopically labeled lipid standard mixture to 43.5 mL 2-propanol (1:60 ratio) and was kept on ice. This cold extraction solvent was added to serum samples in a 3:1 ratio (solvent: serum) for protein precipitation followed by vortex mixing for 15 seconds. Samples were centrifuged at 13,000 rpm for 7 minutes and the resulting supernatant was transferred to LC vials. The supernatant was stored at -80 °C until UHPLC-MS analysis, which was performed within one week of preparation. A blank sample, prepared with LC-MS grade water, underwent the same sample preparation process as the serum samples and was analyzed with the rest of the samples. Pooled quality control (QC) samples were prepared by combining 5-10 μL aliquots of the supernatant of each serum sample. This pooled QC sample was analyzed after every 10 LC-MS runs to monitor instrument stability through the course of the experiment. Samples were randomized for sample preparation and were run in a randomized order on consecutive days.

Combined analysis:

Analysis ID AN004153 AN004154
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Thermo Vanquish Thermo Vanquish
Column Thermo Accucore C30 (150 x 2.1mm,2.6um) Thermo Accucore C30 (150 x 2.1mm,2.6um)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Orbitrap ID-X Tribrid Thermo Orbitrap ID-X Tribrid
Ion Mode NEGATIVE POSITIVE
Units chromatographic peak area chromatographic peak area

Chromatography:

Chromatography ID:CH003073
Instrument Name:Thermo Vanquish
Column Name:Thermo Accucore C30 (150 x 2.1mm,2.6um)
Column Temperature:50
Flow Gradient:0-1 min 80-40% A; 1-5 min 40-30% A; 5-5.5 min 30-15% A; 5.5-8 min 15-10% A; 8-8.2 min 10-0% A; 8.2-10.5 0% A; 10.5-10.7 min 0-80% A; 10.7-12.0 min 80% A.
Flow Rate:0.4 ml min-1
Solvent A:10 mM ammonium acetate with water/acetonitrile (40:60 v/v)
Solvent B:10 mM ammonium acetate with 2-isopropanol/acetonitrile (90:10 v/v). 0.1% formic acid
Chromatography Type:Reversed phase
  
Chromatography ID:CH003074
Instrument Name:Thermo Vanquish
Column Name:Thermo Accucore C30 (150 x 2.1mm,2.6um)
Column Temperature:50
Flow Gradient:0-1 min 80-40% A; 1-5 min 40-30% A; 5-5.5 min 30-15% A; 5.5-8 min 15-10% A; 8-8.2 min 10-0% A; 8.2-10.5 0% A; 10.5-10.7 min 0-80% A; 10.7-12.0 min 80% A.
Flow Rate:0.4 ml min-1
Solvent A:10 mM ammonium formate with water/acetonitrile (40:60 v/v) and 0.1% formic acid
Solvent B:10 mM ammonium formate with 2-isopropanol/acetonitrile (90:10 v/v) and 0.1% formic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS003900
Analysis ID:AN004153
Instrument Name:Thermo Orbitrap ID-X Tribrid
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS data were acquired in the 150-2000 m/z range with a 120,000 mass resolution setting. For MS/MS experiments, the Thermo Scientific Deep AcquireX data acquisition workflow was performed. Stepped normalized collision energy (NCE) of 15,30,45 was used for fragmenting precursor ions in the HCD cell followed by Orbitrap analysis at 30,000 mass resolving power. Precursor ions were also fragmented with CID energy of 40 and were analyzed in the ion trap. Data were processed in Compound Discoverer 3.3.
Ion Mode:NEGATIVE
  
MS ID:MS003901
Analysis ID:AN004154
Instrument Name:Thermo Orbitrap ID-X Tribrid
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS data were acquired in the 150-2000 m/z range with a 120,000 mass resolution setting. The most relevant MS parameters and the chromatographic gradient used are given in supplementary section Table S2 and S3, respectively. For MS/MS experiments, the Thermo Scientific Deep AcquireX data acquisition workflow was performed. Stepped normalized collision energy (NCE) of 15,30,45 was used for fragmenting precursor ions in the HCD cell followed by Orbitrap analysis at 30,000 mass resolving power. Precursor ions were also fragmented with CID energy of 40 and were analyzed in the ion trap.
Ion Mode:POSITIVE
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