Summary of study ST000392

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 PR000306. The data can be accessed directly via it's Project DOI: 10.21228/M8T60D This work is supported by NIH grant, U2C- DK119886.

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

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Study IDST000392
Study TitleSystemic Metabolomic Changes in Blood Samples of Lung Cancer Patients Identified by Gas Chromatography Time-of-Flight Mass Spectrometry
Study SummaryLung cancer is a leading cause of cancer deaths worldwide. Metabolic alterations in tumor cells coupled with systemic indicators of the host response to tumor development have the potential to yield blood profiles with clinical utility for diagnosis and monitoring of treatment. We report results from two separate studies using gas chromatography time-of-flight mass spectrometry (GC-TOF MS) to profile metabolites in human blood samples that significantly differ from non-small cell lung cancer (NSCLC) adenocarcinoma and other lung cancer cases. Metabolomic analysis of blood samples from the two studies yielded a total of 437 metabolites, of which 148 were identified as known compounds and 289 identified as unknown compounds. Differential analysis identified 15 known metabolites in one study and 18 in a second study that were statistically different (p-values <0.05). Levels of maltose, palmitic acid, glycerol, ethanolamine, glutamic acid, and lactic acid were increased in cancer samples while amino acids tryptophan, lysine and histidine decreased. Many of the metabolites were found to be significantly different in both studies, suggesting that metabolomics appears to be robust enough to find systemic changes from lung cancer, thus showing the potential of this type of analysis for lung cancer detection.
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 Date2016-05-09
Total Subjects82
Num Males20
Num Females62
Study CommentsSS = Sigma sample and is used as a quality control
Publicationsdoi: 10.3390/metabo5020192
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/M8T60D
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000306
Project DOI:doi: 10.21228/M8T60D
Project Title:Systemic Metabolomic Changes in Blood Samples of Lung Cancer Patients Identified by Gas Chromatography Time-of-Flight Mass Spectrometry
Project Summary:Lung cancer is a leading cause of cancer deaths worldwide. Metabolic alterations in tumor cells coupled with systemic indicators of the host response to tumor development have the potential to yield blood profiles with clinical utility for diagnosis and monitoring of treatment. We report results from two separate studies using gas chromatography time-of-flight mass spectrometry (GC-TOF MS) to profile metabolites in human blood samples that significantly differ from non-small cell lung cancer (NSCLC) adenocarcinoma and other lung cancer cases. Metabolomic analysis of blood samples from the two studies yielded a total of 437 metabolites, of which 148 were identified as known compounds and 289 identified as unknown compounds. Differential analysis identified 15 known metabolites in one study and 18 in a second study that were statistically different (p-values <0.05). Levels of maltose, palmitic acid, glycerol, ethanolamine, glutamic acid, and lactic acid were increased in cancer samples while amino acids tryptophan, lysine and histidine decreased. Many of the metabolites were found to be significantly different in both studies, suggesting that metabolomics appears to be robust enough to find systemic changes from lung cancer, thus showing the potential of this type of analysis for lung cancer detection.
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: 10.3390/metabo5020192

Subject:

Subject ID:SU000413
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Age Or Age Range:50-92
Gender:M/F
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 Organ Disease State Gender Smoking Status
SA018493140516bjlsa49_1Plasma cancer F Current
SA018494140516bjlsa05_1Plasma cancer F Current
SA018495140516bjlsa27_1Plasma cancer F Former
SA018496140515bjlsa11_1Plasma cancer F Former
SA018497140516bjlsa23_1Plasma cancer F Former
SA018498140516bjlsa19_1Plasma cancer F Former
SA018499140517bjlsa36_1Plasma cancer F Former
SA018500140516bjlsa03_1Plasma cancer F Former
SA018501140518bjlsa32_1Plasma cancer F Former
SA018502140518bjlsa23_2Plasma cancer F Former
SA018503140516bjlsa01_1Plasma cancer M Current
SA018504140516bjlsa41_1Plasma cancer M Current
SA018505140515bjlsa42_1Plasma cancer M Current
SA018506140516bjlsa08_1Plasma cancer M Current
SA018507140517bjlsa25_1Plasma cancer M Current
SA018508140515bjlsa18_1Plasma cancer M Current
SA018509140515bjlsa25_1Plasma cancer M Current
SA018510140517bjlsa43_1Plasma cancer M Current
SA018511140515bjlsa27_1Plasma cancer M Current
SA018512140517bjlsa40_1Plasma cancer M Current
SA018513140518bjlsa19_2Plasma cancer M Current
SA018514140517bjlsa18_1Plasma cancer M Current
SA018515140517bjlsa27_1Plasma cancer M Current
SA018516140516bjlsa21_1Plasma cancer M Current
SA018517140516bjlsa12_1Plasma cancer M Former
SA018518140518bjlsa21_2Plasma cancer M Former
SA018519140517bjlsa03_1Plasma cancer M Former
SA018520140516bjlsa36_1Plasma cancer M Former
SA018521140518bjlsa15_2Plasma cancer M Former
SA018522140515bjlsa22_1Plasma cancer M Former
SA018523140518bjlsa28_1Plasma cancer M Former
SA018524140518bjlsa08_1Plasma cancer M Former
SA018525140518bjlsa30_1Plasma cancer M Former
SA018526140518bjlsa26_1Plasma cancer M Former
SA018527140515bjlsa33_1Plasma cancer M Former
SA018528140516bjlsa43_1Plasma cancer M Former
SA018529140515bjlsa47_1Plasma cancer M Former
SA018530140516bjlsa34_1Plasma cancer M Former
SA018531140517bjlsa34_1Plasma cancer M Former
SA018532140517bjlsa38_1Plasma cancer M Former
SA018533140515bjlsa16_1Plasma cancer M Former
SA018534140516bjlsa25_1Plasma control F Current
SA018535140517bjlsa23_1Plasma control F Current
SA018536140515bjlsa09_1Plasma control F Former
SA018537140518bjlsa04_1Plasma control F Former
SA018538140518bjlsa06_1Plasma control F Former
SA018539140517bjlsa29_1Plasma control F Former
SA018540140518bjlsa10_1Plasma control F Former
SA018541140518bjlsa17_2Plasma control F Former
SA018542140515bjlsa05_1Plasma control F Former
SA018543140518bjlsa01_1Plasma control F Former
SA018544140517bjlsa12_1Plasma control M Current
SA018545140516bjlsa32_1Plasma control M Current
SA018546140515bjlsa20_1Plasma control M Current
SA018547140517bjlsa49_1Plasma control M Current
SA018548140515bjlsa31_1Plasma control M Current
SA018549140515bjlsa07_1Plasma control M Current
SA018550140516bjlsa14_1Plasma control M Current
SA018551140517bjlsa16_1Plasma control M Current
SA018552140516bjlsa16_1Plasma control M Current
SA018553140515bjlsa44_1Plasma control M Current
SA018554140515bjlsa49_1Plasma control M Current
SA018555140515bjlsa14_1Plasma control M Current
SA018556140516bjlsa45_1Plasma control M Current
SA018557140518bjlsa12_1Plasma control M Current
SA018558140515bjlsa29_1Plasma control M Former
SA018559140515bjlsa38_1Plasma control M Former
SA018560140515bjlsa03_1Plasma control M Former
SA018561140516bjlsa38_1Plasma control M Former
SA018562140517bjlsa47_1Plasma control M Former
SA018563140517bjlsa32_1Plasma control M Former
SA018564140516bjlsa10_1Plasma control M Former
SA018565140515bjlsa36_1Plasma control M Former
SA018566140517bjlsa07_1Plasma control M Former
SA018567140516bjlsa30_1Plasma control M Former
SA018568140517bjlsa10_1Plasma control M Former
SA018569140517bjlsa01_1Plasma control M Former
SA018570140517bjlsa45_1Plasma control M Former
SA018571140517bjlsa14_1Plasma control M Former
SA018572140517bjlsa05_1Plasma control M Former
SA018573140517bjlsa21_1Plasma control M Former
SA018574140515bjlsa40_1Plasma control M Former
SA018594140516bjlsa48_1Serum cancer F Current
SA018595140516bjlsa04_1Serum cancer F Current
SA018596140516bjlsa26_1Serum cancer F Former
SA018597140515bjlsa10_1Serum cancer F Former
SA018598140516bjlsa22_1Serum cancer F Former
SA018599140516bjlsa18_1Serum cancer F Former
SA018600140517bjlsa35_1Serum cancer F Former
SA018601140516bjlsa02_1Serum cancer F Former
SA018602140518bjlsa31_1Serum cancer F Former
SA018603140518bjlsa22_2Serum cancer F Former
SA018604140515bjlsa50_1Serum cancer M Current
SA018605140516bjlsa40_1Serum cancer M Current
SA018606140515bjlsa41_1Serum cancer M Current
SA018607140516bjlsa07_1Serum cancer M Current
SA018608140515bjlsa24_1Serum cancer M Current
SA018609140517bjlsa24_1Serum cancer M Current
SA018610140515bjlsa17_1Serum cancer M Current
SA018611140517bjlsa42_1Serum cancer M Current
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Collection:

Collection ID:CO000407
Collection Summary:Pre-existing patient blood samples were acquired from the biorepositories of two institutions (FHCRC and UCDMC), all collected and stored at −80 °C before use in these metabolomics studies. All patient samples for Study 1 (cases) were collected during a clinic visit prior to surgery for resectable early stage lung cancer and the controls were collected from clinic subjects without lung cancer. For Study 2, samples were acquired from University of California at Davis Medical Center (UCDMC) and included a variety of lung cancers. For Study 1, 20 control subjects were compared to 18 cases. Data from two samples were not included in the analysis due to low analytical results for these samples.
Collection Protocol Filename:Metabolomic_Changes_in_Blood_Samples_of_Lung_Cancer_Patients.pdf
Sample Type:Blood
Blood Serum Or Plasma:Both

Treatment:

Treatment ID:TR000427
Treatment Summary:Blood samples (plasma) in Study 1 (FHCRC study) were taken from newly diagnosed lung cancer patients with NSCLC adenocarcinoma (mostly late stage) and were frequency matched with for age, gender and for general smoking history (current and former smokers). Controls for this study were blood samples collected from individuals who were cancer free and with no history of cancer and who were current or former smokers. The second set of blood samples (Study 2) came from patients diagnosed with lung cancers (different types) (11 cases) that were frequency matched (age and gender) with samples from individuals without cancer and with no history of cancer (11 controls). These samples were obtained from the UC Davis Cancer Center Biorepository (CCB) and the UC Davis Clinical laboratory at the UC Davis Medical Center (UCDMC). Smoking history and treatment status were known for most of the cases in Study 2, but not known for some of the control group. Fasting status of patients and controls were unknown. All blood samples (plasma and serum) were prepared using standard clinical SOPs specified at each institution and stored at -80 °C until use.
Treatment Protocol Filename:Metabolomic_Changes_in_Blood_Samples_of_Lung_Cancer_Patients.pdf

Sample Preparation:

Sampleprep ID:SP000420
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 AN000628
Analysis type MS
Chromatography type GC
Chromatography system Agilent 6890N
Column Restek Corporation Rtx-5Sil MS
MS Type EI
MS instrument type GC Ion Trap
MS instrument name Varian 210-MS GC Ion Trap
Ion Mode POSITIVE
Units counts

Chromatography:

Chromatography ID:CH000453
Methods Filename:Data_Dictionary_Fiehn_laboratory_GCTOF_MS_primary_metabolism_10-15-2013_general.pdf
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
Oven Temperature:50°C for 1 min, then ramped at 20°C/min to 330°C, held constant for 5 min
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:MS000561
Analysis ID:AN000628
Instrument Name:Varian 210-MS GC Ion Trap
Instrument Type:GC Ion Trap
MS Type:EI
Ion Mode:POSITIVE
Ion Source Temperature:250 C
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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