Summary of Study ST000390

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.

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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 IDST000390
Study TitleMetabolomic markers of altered nucleotide metabolism in early stage adenocarcinoma (part I)
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)peg
Analysis Type DetailGC-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

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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:SU000411
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
SA018330121129bbdsa05_1F Current Smoker adenocarcinoma No
SA018331121129bbdsa33_1F Current Smoker adenocarcinoma Yes
SA018328121130bbdsa17_1F Current Smoker adenocarcinoma w/ BAC No
SA018329121130bbdsa21_1F Current Smoker adenocarcinoma w/ BAC Yes
SA018356121130bbdsa27_1F Ex-Smoker adenocarcinoma, multiple primaries No
SA018357121129bbdsa12_1F Ex-Smoker adenocarcinoma, multiple primaries No
SA018358121129bbdsa24_1F Ex-Smoker adenocarcinoma, multiple primaries Yes
SA018359121130bbdsa07_1F Ex-Smoker adenocarcinoma, multiple primaries Yes
SA018360121129bbdsa50_1F Ex-Smoker adenocarcinoma No
SA018361121129bbdsa34_1F Ex-Smoker adenocarcinoma No
SA018362121129bbdsa10_1F Ex-Smoker adenocarcinoma No
SA018363121130bbdsa12_1F Ex-Smoker adenocarcinoma No
SA018364121129bbdsa22_1F Ex-Smoker adenocarcinoma No
SA018365121130bbdsa05_1F Ex-Smoker adenocarcinoma No
SA018366121130bbdsa34_1F Ex-Smoker adenocarcinoma No
SA018367121129bbdsa17_1F Ex-Smoker adenocarcinoma No
SA018336121129bbdsa41_1F Ex-Smoker Adenocarcinoma No
SA018368121130bbdsa20_1F Ex-Smoker adenocarcinoma Yes
SA018369121129bbdsa13_1F Ex-Smoker adenocarcinoma Yes
SA018370121129bbdsa15_1F Ex-Smoker adenocarcinoma Yes
SA018371121130bbdsa09_1F Ex-Smoker adenocarcinoma Yes
SA018372121130bbdsa14_1F Ex-Smoker adenocarcinoma Yes
SA018373121130bbdsa01_1F Ex-Smoker adenocarcinoma Yes
SA018374121130bbdsa16_1F Ex-Smoker adenocarcinoma Yes
SA018375121130bbdsa06_1F Ex-Smoker adenocarcinoma Yes
SA018337121129bbdsa32_1F Ex-Smoker Adenocarcinoma Yes
SA018350121129bbdsa27_1F Ex-Smoker adenocarcinoma w/ bac No
SA018338121129bbdsa43_1F Ex-Smoker adenocarcinoma w/ BAC No
SA018339121130bbdsa11_1F Ex-Smoker adenocarcinoma w/ BAC No
SA018340121129bbdsa08_1F Ex-Smoker adenocarcinoma w/ BAC No
SA018341121129bbdsa26_1F Ex-Smoker adenocarcinoma w/ BAC No
SA018342121129bbdsa23_1F Ex-Smoker adenocarcinoma w/ BAC No
SA018343121129bbdsa06_1F Ex-Smoker adenocarcinoma w/ BAC No
SA018352121130bbdsa02_1F Ex-Smoker adenocarcinoma w/BAC No
SA018353121129bbdsa37_1F Ex-Smoker adenocarcinoma w/BAC No
SA018332121129bbdsa21_1F Ex-Smoker Adenocarcinoma w/ BAC No
SA018333121130bbdsa25_1F Ex-Smoker Adenocarcinoma w/ BAC No
SA018351121129bbdsa31_1F Ex-Smoker adenocarcinoma w/ bac Yes
SA018344121129bbdsa04_1F Ex-Smoker adenocarcinoma w/ BAC Yes
SA018345121130bbdsa35_1F Ex-Smoker adenocarcinoma w/ BAC Yes
SA018346121129bbdsa25_1F Ex-Smoker adenocarcinoma w/ BAC Yes
SA018347121130bbdsa03_1F Ex-Smoker adenocarcinoma w/ BAC Yes
SA018348121129bbdsa02_1F Ex-Smoker adenocarcinoma w/ BAC Yes
SA018349121129bbdsa44_1F Ex-Smoker adenocarcinoma w/ BAC Yes
SA018354121129bbdsa16_1F Ex-Smoker adenocarcinoma w/BAC Yes
SA018355121130bbdsa24_1F Ex-Smoker adenocarcinoma w/BAC Yes
SA018334121130bbdsa29_1F Ex-Smoker Adenocarcinoma w/ BAC Yes
SA018335121130bbdsa04_1F Ex-Smoker Adenocarcinoma w/ BAC Yes
SA018378121130bbdsa19_1M Current Smoker adenocarcinoma No
SA018379121129bbdsa48_1M Current Smoker adenocarcinoma No
SA018380121129bbdsa46_1M Current Smoker adenocarcinoma Yes
SA018381121130bbdsa23_1M Current Smoker adenocarcinoma Yes
SA018376121129bbdsa39_1M Current Smoker adenocarcinoma w/ BAC No
SA018377121130bbdsa08_1M Current Smoker adenocarcinoma w/ BAC Yes
SA018400121129bbdsa47_1M Ex-Smoker adenocarcinoma No
SA018401121130bbdsa31_1M Ex-Smoker adenocarcinoma No
SA018402121130bbdsa22_1M Ex-Smoker adenocarcinoma No
SA018382121129bbdsa38_1M Ex-Smoker Adenocarcinoma No
SA018403121129bbdsa40_1M Ex-Smoker adenocarcinoma Yes
SA018404121130bbdsa36_1M Ex-Smoker adenocarcinoma Yes
SA018405121129bbdsa11_1M Ex-Smoker adenocarcinoma Yes
SA018383121130bbdsa13_1M Ex-Smoker Adenocarcinoma Yes
SA018384121129bbdsa01_1M Ex-Smoker adenocarcinoma w/ BAC No
SA018385121129bbdsa45_1M Ex-Smoker adenocarcinoma w/ BAC No
SA018386121130bbdsa10_1M Ex-Smoker adenocarcinoma w/ BAC No
SA018387121129bbdsa14_1M Ex-Smoker adenocarcinoma w/ BAC No
SA018388121130bbdsa37_1M Ex-Smoker adenocarcinoma w/ BAC No
SA018389121129bbdsa09_1M Ex-Smoker adenocarcinoma w/ BAC No
SA018390121129bbdsa18_1M Ex-Smoker adenocarcinoma w/ BAC No
SA018391121129bbdsa35_1M Ex-Smoker adenocarcinoma w/ BAC No
SA018392121129bbdsa30_1M Ex-Smoker adenocarcinoma w/ BAC Yes
SA018393121129bbdsa29_1M Ex-Smoker adenocarcinoma w/ BAC Yes
SA018394121130bbdsa30_1M Ex-Smoker adenocarcinoma w/ BAC Yes
SA018395121130bbdsa15_1M Ex-Smoker adenocarcinoma w/ BAC Yes
SA018396121129bbdsa07_1M Ex-Smoker adenocarcinoma w/ BAC Yes
SA018397121130bbdsa26_1M Ex-Smoker adenocarcinoma w/ BAC Yes
SA018398121130bbdsa18_1M Ex-Smoker adenocarcinoma w/ BAC Yes
SA018399121130bbdsa32_1M Ex-Smoker adenocarcinoma w/ BAC Yes
SA018319121130bbdsa33_1- - - -
SA018320121129bbdsa19_1- - - -
SA018321121130bbdsa28_1- - - -
SA018322121129bbdsa49_1- - - -
SA018323121129bbdsa03_1- - - -
SA018324121129bbdsa20_1- - - -
SA018325121129bbdsa42_1- - - -
SA018326121129bbdsa28_1- - - -
SA018327121129bbdsa36_1- - - -
Showing results 1 to 87 of 87

Collection:

Collection ID:CO000405
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:TR000425
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:SP000418
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 AN000626
Analysis type MS
Chromatography type GC
Chromatography system Agilent 6890N
Column Restek Corporation Rtx-5Sil MS
MS Type EI
MS instrument type GC-TOF
MS instrument name Leco Pegasus III GC TOF
Ion Mode POSITIVE
Units counts

Chromatography:

Chromatography ID:CH000451
Instrument Name:Agilent 6890N
Column Name:Restek Corporation Rtx-5Sil MS
Column Pressure:7.7 PSI
Column Temperature:50-330C
Flow Rate:1 ml/min
Injection Temperature:50 C ramped to 250 C by 12 C/s
Sample Injection:0.5 uL
Transferline Temperature:230C
Washing Buffer:Ethyl Acetate
Sample Loop Size:30 m length x 0.25 mm internal diameter
Randomization Order:Excel generated
Chromatography Type:GC

MS:

MS ID:MS000559
Analysis ID:AN000626
Instrument Name:Leco Pegasus III GC TOF
Instrument Type:GC-TOF
MS Type:EI
Ion Mode:POSITIVE
Ion Source Temperature:250 C
Ionization:Pos
Ionization Energy:70 eV
Mass Accuracy:Nominal
Source Temperature:250 C
Scan Range Moverz:85-500 Da
Scanning Cycle:17 Hz
Scanning Range:85-500 Da
Skimmer Voltage:1850 V
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