Summary of Study ST000391

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 PR000305. The data can be accessed directly via it's Project DOI: 10.21228/M8PG66 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 IDST000391
Study TitleMetabolomic markers of altered nucleotide metabolism in early stage adenocarcinoma (part II)
Study SummaryLung cancer has been the leading cause of cancer death in the United States and worldwide for many decades. Low dose spiral computerized tomography (LDCT) is likely to become the first approved screening and early detection test in the upcoming year, but it is plagued by a high false-positive rate. There is a need to develop complementary screening and early detection tools. A blood-based lung cancer signature is an attractive solution. Given that our knowledge of the molecular biology of smoking-induced lung cancer has dramatically increased over the past few years, this approach is plausible. To date, this effort has been focused on the identification of genomic and proteomic signatures with limited success. A broader strategy that incorporates additional cancer traits is needed. It is well recognized that wide coverage of cellular metabolism in cancer could help provide valuable diagnostic biomarkers and potentially identify molecular drivers of tumorigenesis. Recent advances in mass spectrometry have enabled comprehensive metabolomic analyses of lipids, carbohydrates, amino acids, and nucleotides within a variety of biologic matrices. Early evidence from metabolomic investigation of cancer has identified many altered biochemical profiles. However, to date, there have been few investigations of lung cancer, and most studies have looked at blood plasma or were limited by small sample sizes with mixed histologies. In the current investigation, gas chromatography time-offlight mass spectrometry (GC-TOF) was used to measure 462 lipid, carbohydrate, amino acid, organic acid, and nucleotide metabolites in 39 malignant and nonmalignant lung tissue pairs from current or former smokers with early stage adenocarcinoma. This study cohort represents patient characteristics and tumor histology most likely to be detected with LDCT screening. We hypothesize that identification of cancer-induced cellular and tissue level biochemical changes can offer a robust method for identification of candidate circulating biomarkers and improve our understanding of biochemical changes involved in adenocarcinoma tumorigenesis.
Institute
University of California, Davis
DepartmentGenome and Biomedical Sciences Facility
LaboratoryWCMC Metabolomics Core
Last NameFiehn
First NameOliver
Address1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Emailofiehn@ucdavis.edu
Phone(530) 754-8258
Submit Date2016-05-06
Publicationsdoi: 10.1158/1940-6207
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2016-06-18
Release Version2
Release CommentsUpdated study design factors
Oliver Fiehn Oliver Fiehn
https://dx.doi.org/10.21228/M8PG66
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Project:

Project ID:PR000305
Project DOI:doi: 10.21228/M8PG66
Project Title:Metabolomic markers of altered nucleotide metabolism in early stage adenocarcinoma
Project Summary:Lung cancer has been the leading cause of cancer death in the United States and worldwide for many decades. Low dose spiral computerized tomography (LDCT) is likely to become the first approved screening and early detection test in the upcoming year, but it is plagued by a high false-positive rate. There is a need to develop complementary screening and early detection tools. A blood-based lung cancer signature is an attractive solution. Given that our knowledge of the molecular biology of smoking-induced lung cancer has dramatically increased over the past few years, this approach is plausible. To date, this effort has been focused on the identification of genomic and proteomic signatures with limited success. A broader strategy that incorporates additional cancer traits is needed. It is well recognized that wide coverage of cellular metabolism in cancer could help provide valuable diagnostic biomarkers and potentially identify molecular drivers of tumorigenesis. Recent advances in mass spectrometry have enabled comprehensive metabolomic analyses of lipids, carbohydrates, amino acids, and nucleotides within a variety of biologic matrices. Early evidence from metabolomic investigation of cancer has identified many altered biochemical profiles. However, to date, there have been few investigations of lung cancer, and most studies have looked at blood plasma or were limited by small sample sizes with mixed histologies. In the current investigation, gas chromatography time-offlight mass spectrometry (GC-TOF) was used to measure 462 lipid, carbohydrate, amino acid, organic acid, and nucleotide metabolites in 39 malignant and nonmalignant lung tissue pairs from current or former smokers with early stage adenocarcinoma. This study cohort represents patient characteristics and tumor histology most likely to be detected with LDCT screening. We hypothesize that identification of cancer-induced cellular and tissue level biochemical changes can offer a robust method for identification of candidate circulating biomarkers and improve our understanding of biochemical changes involved in adenocarcinoma tumorigenesis.
Institute:University of California, Davis
Department:Genome and Biomedical Sciences Facility
Laboratory:WCMC Metabolomics Core
Last Name:Fiehn
First Name:Oliver
Address:1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Email:ofiehn@ucdavis.edu
Phone:(530) 754-8258
Funding Source:NIH U24DK097154
Publications:doi: 10.1158/1940-6207

Subject:

Subject ID:SU000412
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Age Or Age Range:55-91
Gender:M/F
Human Race:Caucasian, Asian
Human Smoking Status:Current vs. former
Species Group:Human

Factors:

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

mb_sample_id local_sample_id Sex Smoking Status Diagnosis Tumor Present
SA018417120412_lung_tissue_Sample37F Current Smoker adenocarcinoma No
SA018418120412_lung_tissue_Sample75F Current Smoker adenocarcinoma Yes
SA018415120412_lung_tissue_Sample33F Current Smoker adenocarcinoma w/ BAC No
SA018416120412_lung_tissue_Sample26F Current Smoker adenocarcinoma w/ BAC Yes
SA018443120412_lung_tissue_Sample72F Ex-Smoker adenocarcinoma, multiple primaries No
SA018444120412_lung_tissue_Sample50F Ex-Smoker adenocarcinoma, multiple primaries No
SA018445120412_lung_tissue_Sample70F Ex-Smoker adenocarcinoma, multiple primaries Yes
SA018446120412_lung_tissue_Sample65F Ex-Smoker adenocarcinoma, multiple primaries Yes
SA018447120412_lung_tissue_Sample63F Ex-Smoker adenocarcinoma No
SA018448120412_lung_tissue_Sample47F Ex-Smoker adenocarcinoma No
SA018449120412_lung_tissue_Sample27F Ex-Smoker adenocarcinoma No
SA018450120412_lung_tissue_Sample32F Ex-Smoker adenocarcinoma No
SA018451120412_lung_tissue_Sample73F Ex-Smoker adenocarcinoma No
SA018452120412_lung_tissue_Sample90F Ex-Smoker adenocarcinoma No
SA018453120412_lung_tissue_Sample25F Ex-Smoker adenocarcinoma No
SA018454120412_lung_tissue_Sample97F Ex-Smoker adenocarcinoma No
SA018423120412_lung_tissue_Sample44F Ex-Smoker Adenocarcinoma No
SA018455120412_lung_tissue_Sample59F Ex-Smoker adenocarcinoma Yes
SA018456120412_lung_tissue_Sample8F Ex-Smoker adenocarcinoma Yes
SA018457120412_lung_tissue_Sample12F Ex-Smoker adenocarcinoma Yes
SA018458120412_lung_tissue_Sample6F Ex-Smoker adenocarcinoma Yes
SA018459120412_lung_tissue_Sample69F Ex-Smoker adenocarcinoma Yes
SA018460120412_lung_tissue_Sample43F Ex-Smoker adenocarcinoma Yes
SA018461120412_lung_tissue_Sample61F Ex-Smoker adenocarcinoma Yes
SA018462120412_lung_tissue_Sample29F Ex-Smoker adenocarcinoma Yes
SA018424120412_lung_tissue_Sample87F Ex-Smoker Adenocarcinoma Yes
SA018437120412_lung_tissue_Sample28F Ex-Smoker adenocarcinoma w/ bac No
SA018425120412_lung_tissue_Sample71F Ex-Smoker adenocarcinoma w/ BAC No
SA018426120412_lung_tissue_Sample17F Ex-Smoker adenocarcinoma w/ BAC No
SA018427120412_lung_tissue_Sample34F Ex-Smoker adenocarcinoma w/ BAC No
SA018428120412_lung_tissue_Sample11F Ex-Smoker adenocarcinoma w/ BAC No
SA018429120412_lung_tissue_Sample95F Ex-Smoker adenocarcinoma w/ BAC No
SA018430120412_lung_tissue_Sample35F Ex-Smoker adenocarcinoma w/ BAC No
SA018439120412_lung_tissue_Sample36F Ex-Smoker adenocarcinoma w/BAC No
SA018440120412_lung_tissue_Sample2F Ex-Smoker adenocarcinoma w/BAC No
SA018419120412_lung_tissue_Sample100F Ex-Smoker Adenocarcinoma w/ BAC No
SA018420120412_lung_tissue_Sample89F Ex-Smoker Adenocarcinoma w/ BAC No
SA018438120412_lung_tissue_Sample94F Ex-Smoker adenocarcinoma w/ bac Yes
SA018431120412_lung_tissue_Sample20F Ex-Smoker adenocarcinoma w/ BAC Yes
SA018432120412_lung_tissue_Sample31F Ex-Smoker adenocarcinoma w/ BAC Yes
SA018433120412_lung_tissue_Sample45F Ex-Smoker adenocarcinoma w/ BAC Yes
SA018434120412_lung_tissue_Sample52F Ex-Smoker adenocarcinoma w/ BAC Yes
SA018435120412_lung_tissue_Sample18F Ex-Smoker adenocarcinoma w/ BAC Yes
SA018436120412_lung_tissue_Sample40F Ex-Smoker adenocarcinoma w/ BAC Yes
SA018441120412_lung_tissue_Sample54F Ex-Smoker adenocarcinoma w/BAC Yes
SA018442120412_lung_tissue_Sample30F Ex-Smoker adenocarcinoma w/BAC Yes
SA018421120412_lung_tissue_Sample49F Ex-Smoker Adenocarcinoma w/ BAC Yes
SA018422120412_lung_tissue_Sample13F Ex-Smoker Adenocarcinoma w/ BAC Yes
SA018465120412_lung_tissue_Sample62M Current Smoker adenocarcinoma No
SA018466120412_lung_tissue_Sample46M Current Smoker adenocarcinoma No
SA018467120412_lung_tissue_Sample5M Current Smoker adenocarcinoma Yes
SA018468120412_lung_tissue_Sample81M Current Smoker adenocarcinoma Yes
SA018463120412_lung_tissue_Sample91M Current Smoker adenocarcinoma w/ BAC No
SA018464120412_lung_tissue_Sample56M Current Smoker adenocarcinoma w/ BAC Yes
SA018487120412_lung_tissue_Sample4M Ex-Smoker adenocarcinoma No
SA018488120412_lung_tissue_Sample74M Ex-Smoker adenocarcinoma No
SA018489120412_lung_tissue_Sample10M Ex-Smoker adenocarcinoma No
SA018469120412_lung_tissue_Sample55M Ex-Smoker Adenocarcinoma No
SA018490120412_lung_tissue_Sample39M Ex-Smoker adenocarcinoma Yes
SA018491120412_lung_tissue_Sample93M Ex-Smoker adenocarcinoma Yes
SA018492120412_lung_tissue_Sample79M Ex-Smoker adenocarcinoma Yes
SA018470120412_lung_tissue_Sample68M Ex-Smoker Adenocarcinoma Yes
SA018471120412_lung_tissue_Sample1M Ex-Smoker adenocarcinoma w/ BAC No
SA018472120412_lung_tissue_Sample15M Ex-Smoker adenocarcinoma w/ BAC No
SA018473120412_lung_tissue_Sample14M Ex-Smoker adenocarcinoma w/ BAC No
SA018474120412_lung_tissue_Sample24M Ex-Smoker adenocarcinoma w/ BAC No
SA018475120412_lung_tissue_Sample80M Ex-Smoker adenocarcinoma w/ BAC No
SA018476120412_lung_tissue_Sample84M Ex-Smoker adenocarcinoma w/ BAC No
SA018477120412_lung_tissue_Sample53M Ex-Smoker adenocarcinoma w/ BAC No
SA018478120412_lung_tissue_Sample78M Ex-Smoker adenocarcinoma w/ BAC No
SA018479120412_lung_tissue_Sample58M Ex-Smoker adenocarcinoma w/ BAC Yes
SA018480120412_lung_tissue_Sample83M Ex-Smoker adenocarcinoma w/ BAC Yes
SA018481120412_lung_tissue_Sample64M Ex-Smoker adenocarcinoma w/ BAC Yes
SA018482120412_lung_tissue_Sample96M Ex-Smoker adenocarcinoma w/ BAC Yes
SA018483120412_lung_tissue_Sample66M Ex-Smoker adenocarcinoma w/ BAC Yes
SA018484120412_lung_tissue_Sample85M Ex-Smoker adenocarcinoma w/ BAC Yes
SA018485120412_lung_tissue_Sample3M Ex-Smoker adenocarcinoma w/ BAC Yes
SA018486120412_lung_tissue_Sample19M Ex-Smoker adenocarcinoma w/ BAC Yes
SA018406005_120412_lung_tissue_LungTissuePoolMS- - - -
SA018407006_120412_lung_tissue_LungTissuePoolMS- - - -
SA018408004_120412_lung_tissue_LungTissuePoolMS- - - -
SA018409002_120412_lung_tissue_LungTissuePoolMS- - - -
SA018410001_120412_lung_tissue_LungTissuePoolMS- - - -
SA018411007_120412_lung_tissue_LungTissuePoolMS- - - -
SA018412003_120412_lung_tissue_LungTissuePoolMS- - - -
SA018413009_120412_lung_tissue_LungTissuePoolMS- - - -
SA018414008_120412_lung_tissue_LungTissuePoolMS- - - -
Showing results 1 to 87 of 87

Collection:

Collection ID:CO000406
Collection Summary:Deidentified malignant and adjacent nonmalignant lung tissue was obtained from the New York University biorepository. Residual tumor and adjacent nonmalignant tissue was harvested from the resected lung after routine pathologic protocols were completed, following an approved Institutional Review Board (IRB) protocol with patient consent. Two to three tissue pieces were aliquoted into 1.5 mL Nunc vials, and then immediately placed in liquid nitrogen. After transport in liquid nitrogen, each vial was barcoded and stored at 80 C until analyzed.
Collection Protocol Filename:Cancer_Prev_Res-2015-Wikoff-410-8.pdf
Sample Type:Tissue

Treatment:

Treatment ID:TR000426
Treatment Summary:All specimens were clinically annotated for age, gender, race, histology, smoking status, pack-years, and stage of disease. For this clinical study, samples were selected that came from patients who met the following criteria: (i) current or former smokers, (ii) adenocarcinoma histology, (iii) pathologic stage IA or IB, and (iv) had understood and signed the IRB consent form.
Treatment Protocol Filename:Cancer_Prev_Res-2015-Wikoff-410-8.pdf

Sample Preparation:

Sampleprep ID:SP000419
Sampleprep Summary:1. Switch on bath to pre-cool at –20°C (±2°C validity temperature range) 2. Gently rotate or aspirate the blood samples for about 10s to obtain a homogenised sample. 3. Aliquot 30μl of plasma sample to a 1.0 mL extraction solution. The extraction solution has to be prechilled using the ThermoElectron Neslab RTE 740 cooling bath set to -20°C. 4. Vortex the sample for about 10s and shake for 5 min at 4°C using the Orbital Mixing Chilling/Heating Plate. If you are using more than one sample, keep the rest of the sample on ice (chilled at <0°C with sodium chloride). 5. Centrifuge samples for 2min at 14000 rcf using the centrifuge Eppendorf 5415 D. 6. Aliquot two 450μL portions of the supernatant. One for analysis and one for a backup sample. Store the backup aliquot in -20°C freezer. 7. Evaporate one 450μL aliquots of the sample in the Labconco Centrivap cold trap concentrator to complete dryness. 8. The dried aliquot is then re-suspended with 450 μL 50% acetonitrile (degassed as given above). 9. Centrifuged for 2 min at 14000 rcf using the centrifuge Eppendorf 5415. 10. Remove supernatant to a new Eppendorf tube. 11. Evaporate the supernatant to dryness in the Labconco Centrivap cold trap concentrator. 12. Submit to derivatization.
Sampleprep Protocol Filename:SOP_blood-GCTOF-11082012.pdf

Combined analysis:

Analysis ID AN000627
Analysis type MS
Chromatography type HILIC
Chromatography system Agilent 6530
Column Waters Acquity BEH HILIC (150 x 2.1mm,1.7um)
MS Type ESI
MS instrument type QTOF
MS instrument name Agilent 6530A QTOF
Ion Mode POSITIVE
Units counts

Chromatography:

Chromatography ID:CH000452
Methods Filename:LungNodule_HILIC_Pos_101_AcqMethodReport.pdf
Instrument Name:Agilent 6530
Column Name:Waters Acquity BEH HILIC (150 x 2.1mm,1.7um)
Column Pressure:1200 bar
Column Temperature:45 C
Flow Gradient:100%B to 45% B
Flow Rate:0.4 mL/min
Sample Injection:5uL
Solvent A:100% water; 4 mM acetic acid; 6 mM ammonium acetate
Solvent B:90% acetonitrile/10% water; 4 mM acetic acid; 6 mM ammonium acetate
Analytical Time:20 min
Randomization Order:Excel generated
Chromatography Type:HILIC

MS:

MS ID:MS000560
Analysis ID:AN000627
Instrument Name:Agilent 6530A QTOF
Instrument Type:QTOF
MS Type:ESI
Ion Mode:POSITIVE
Capillary Voltage:3000 V
Dry Gas Flow:8 L/min
Dry Gas Temp:350 C
Fragment Voltage:125 V
Ionization:Pos
Mass Accuracy:Nominal
Nebulizer:35 psig
Octpole Voltage:750 V
Scanning Cycle:2 Hz
Scanning Range:57-1400 Da
Skimmer Voltage:65 V
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