Summary of Study ST000385

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 PR000302. The data can be accessed directly via it's Project DOI: 10.21228/M80W30 This work is supported by NIH grant, U2C- DK119886.

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Study IDST000385
Study TitleInvestigation of metabolomic blood biomarkers for detection of adenocarcinoma lung cancer (training set)
Study SummaryRecently, the National Lung Cancer Screen Trial (NLST) demonstrated that low-dose CT (LDCT) screening could reduce mortality due to lung cancer by 20%. However, LDCT screening is largely hindered by high false-positive rates (96%), particularly in high-risk populations (heavy smokers), due to the low prevalence rates (less than 2%) of malignant tumors and high incidence of benign lung nodules. Consequently, complementary biomarkers that can be used in conjunction with LDCT screening to improve diagnostic capacities and reduce false-positive rates are highly desirable. Preferably, such complementary tools should be noninvasive and exhibit high sensitivity and specificity. The application of “-omic” sciences (genomics, transcriptomics, proteomics, and metabolomics) represents valuable tools for the discovery and validation of potential biomarkers that can be used for detection of NSCLC. Of these omic sciences, metabolomics has received considerable attention for its application in cancer. Metabolomics is the assessment of small molecules and biochemical intermediates (metabolites) using analytic instrumentation. Metabolites in blood are the product of all cellular processes, which are highly responsive to conditions of disease and environment, and represent the final output products of all organs forming a detailed systemic representation of an individual's current physiologic state. In this study, we used an untargeted metabolomics approach using gas chromatography time-of-flight mass spectrometry (GCTOFMS) to analyze the metabolome of serum and plasma samples both collected from the same patients that were organized into two independent case–control studies (ADC1 and ADC2). In both studies, only NSCLC adenocarcinoma was investigated. The overall objectives were to (i) determine whether individual or combinations of metabolites could be used as a diagnostic test to distinguish NSCLC adenocarcinoma from controls and (ii) to determine which, plasma or serum, provides more accurate classifiers for the detection of lung cancer. We developed individual and multimetabolite classifiers using a training test from the ADC1 study and evaluated the performance of the constructed classifiers, individually or in combination, in an independent test/validation study (ADC2). This study shows the potential of metabolite-based diagnostic tests for detection of lung adenocarcinoma. Further validation in a larger pool of samples is warranted.
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 Date2016-10-04
Study CommentsSS = Sigma sample and is used as a quality control The first set (ADC1) used for biomarker development consisted of serum and plasma samples obtained from 52 stages I–IV NSCLC adenocarcinoma patients (52 plasma and 49 serum), and 31 healthy controls (31 pairs of serum and plasma) for a total of 163 samples. This set was regarded as the training set for biomarker discovery and classifier development. A second, independent case–control study (ADC2) consisting of serum and plasma samples collected from 43 stage I–IV NSCLC adenocarcinoma patients and 43 healthy controls (total 172 samples) was used as an independent test set for biomarker evaluation. A limitation of this study is the relatively small sample size for each cohort (52 cases, 31 controls for ADC1, and 43 cases and 43 controls for ADC2) because patient variability can be a big factor in smaller studies.
Raw Data AvailableYes
Analysis Type DetailGC-MS
Release Date2016-04-30
Release Version1
Oliver Fiehn Oliver Fiehn
https://dx.doi.org/10.21228/M80W30
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR000302
Project DOI:doi: 10.21228/M80W30
Project Title:Study1 Investigation of metabolomic blood biomarkers for detection of adenocarcinoma lung cancer
Project Summary:Recently, the National Lung Cancer Screen Trial (NLST) demonstrated that low-dose CT (LDCT) screening could reduce mortality due to lung cancer by 20%. However, LDCT screening is largely hindered by high false-positive rates (96%), particularly in high-risk populations (heavy smokers), due to the low prevalence rates (less than 2%) of malignant tumors and high incidence of benign lung nodules. Consequently, complementary biomarkers that can be used in conjunction with LDCT screening to improve diagnostic capacities and reduce false-positive rates are highly desirable. Preferably, such complementary tools should be noninvasive and exhibit high sensitivity and specificity. The application of “-omic” sciences (genomics, transcriptomics, proteomics, and metabolomics) represents valuable tools for the discovery and validation of potential biomarkers that can be used for detection of NSCLC. Of these omic sciences, metabolomics has received considerable attention for its application in cancer. Metabolomics is the assessment of small molecules and biochemical intermediates (metabolites) using analytic instrumentation. Metabolites in blood are the product of all cellular processes, which are highly responsive to conditions of disease and environment, and represent the final output products of all organs forming a detailed systemic representation of an individual's current physiologic state. In this study, we used an untargeted metabolomics approach using gas chromatography time-of-flight mass spectrometry (GCTOFMS) to analyze the metabolome of serum and plasma samples both collected from the same patients that were organized into two independent case–control studies (ADC1 and ADC2). In both studies, only NSCLC adenocarcinoma was investigated. The overall objectives were to (i) determine whether individual or combinations of metabolites could be used as a diagnostic test to distinguish NSCLC adenocarcinoma from controls and (ii) to determine which, plasma or serum, provides more accurate classifiers for the detection of lung cancer. We developed individual and multimetabolite classifiers using a training test from the ADC1 study and evaluated the performance of the constructed classifiers, individually or in combination, in an independent test/validation study (ADC2). This study shows the potential of metabolite-based diagnostic tests for detection of lung adenocarcinoma. Further validation in a larger pool of samples is warranted.
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

Subject:

Subject ID:SU000406
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Species Group:Human

Factors:

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

mb_sample_id local_sample_id Organ Health State Smoking Status Gender
SA017481140227dlvsa36_1Plasma Adenocarcinoma Current F
SA017482140226dlvsa30_1Plasma Adenocarcinoma Current F
SA017483140226dlvsa36_1Plasma Adenocarcinoma Current F
SA017484140227dlvsa47_1Plasma Adenocarcinoma Current F
SA017485140228dlvsa08_1Plasma Adenocarcinoma Current F
SA017486140228dlvsa30_1Plasma Adenocarcinoma Current F
SA017487140228dlvsa17_1Plasma Adenocarcinoma Current F
SA017488140225dlvsa44_1Plasma Adenocarcinoma Current F
SA017489140228dlvsa39_1Plasma Adenocarcinoma Current F
SA017490140225dlvsa14_1Plasma Adenocarcinoma Current M
SA017491140226dlvsa21_1Plasma Adenocarcinoma Current M
SA017492140226dlvsa41_1Plasma Adenocarcinoma Current M
SA017493140225dlvsa31_1Plasma Adenocarcinoma Current M
SA017494140228dlvsa28_1Plasma Adenocarcinoma Current M
SA017495140227dlvsa14_1Plasma Adenocarcinoma Current M
SA017496140225dlvsa05_1Plasma Adenocarcinoma Former F
SA017497140225dlvsa09_1Plasma Adenocarcinoma Former F
SA017498140225dlvsa07_1Plasma Adenocarcinoma Former F
SA017499140225dlvsa22_1Plasma Adenocarcinoma Former F
SA017500140226dlvsa03_1Plasma Adenocarcinoma Former F
SA017501140227dlvsa40_1Plasma Adenocarcinoma Former F
SA017502140226dlvsa23_1Plasma Adenocarcinoma Former F
SA017503140226dlvsa43_1Plasma Adenocarcinoma Former F
SA017504140228dlvsa26_1Plasma Adenocarcinoma Former F
SA017505140225dlvsa18_1Plasma Adenocarcinoma Former F
SA017506140228dlvsa19_1Plasma Adenocarcinoma Former F
SA017507140227dlvsa03_1Plasma Adenocarcinoma Former F
SA017508140228dlvsa06_1Plasma Adenocarcinoma Former F
SA017509140225dlvsa16_1Plasma Adenocarcinoma Former F
SA017510140228dlvsa12_1Plasma Adenocarcinoma Former F
SA017511140227dlvsa18_1Plasma Adenocarcinoma Former M
SA017512140227dlvsa21_1Plasma Adenocarcinoma Former M
SA017513140228dlvsa34_1Plasma Adenocarcinoma Former M
SA017514140226dlvsa27_1Plasma Adenocarcinoma Former M
SA017515140228dlvsa37_1Plasma Adenocarcinoma Former M
SA017516140225dlvsa36_1Plasma Adenocarcinoma Former M
SA017517140228dlvsa23_1Plasma Adenocarcinoma Former M
SA017518140227dlvsa01_1Plasma Adenocarcinoma Former M
SA017519140227dlvsa45_1Plasma Adenocarcinoma Former M
SA017520140228dlvsa21_1Plasma Adenocarcinoma Former M
SA017521140227dlvsa49_1Plasma Adenocarcinoma Former M
SA017522140226dlvsa16_1Plasma Adenocarcinoma Former M
SA017523140226dlvsa49_1Plasma Adenocarcinoma Former M
SA017524140225dlvsa33_1Plasma Healthy Current F
SA017525140227dlvsa16_1Plasma Healthy Current F
SA017526140227dlvsa25_1Plasma Healthy Current F
SA017527140225dlvsa49_1Plasma Healthy Current F
SA017528140226dlvsa12_1Plasma Healthy Current F
SA017529140225dlvsa25_1Plasma Healthy Current F
SA017530140226dlvsa14_1Plasma Healthy Current F
SA017531140227dlvsa10_1Plasma Healthy Current F
SA017532140227dlvsa07_1Plasma Healthy Current F
SA017533140225dlvsa40_1Plasma Healthy Current M
SA017534140226dlvsa08_1Plasma Healthy Current M
SA017535140228dlvsa15_1Plasma Healthy Current M
SA017536140225dlvsa27_1Plasma Healthy Current M
SA017537140227dlvsa43_1Plasma Healthy Current M
SA017538140227dlvsa34_1Plasma Healthy Current M
SA017539140227dlvsa32_1Plasma Healthy Current M
SA017540140227dlvsa29_1Plasma Healthy Former F
SA017541140228dlvsa01_1Plasma Healthy Former F
SA017542140225dlvsa42_1Plasma Healthy Former F
SA017543140225dlvsa20_1Plasma Healthy Former F
SA017544140226dlvsa34_1Plasma Healthy Former F
SA017545140226dlvsa45_1Plasma Healthy Former F
SA017546140226dlvsa05_1Plasma Healthy Former F
SA017547140228dlvsa04_1Plasma Healthy Former F
SA017548140225dlvsa03_1Plasma Healthy Former F
SA017549140227dlvsa23_1Plasma Healthy Former F
SA017550140228dlvsa10_1Plasma Healthy Former F
SA017551140226dlvsa19_1Plasma Healthy Former F
SA017552140226dlvsa10_1Plasma Healthy Former F
SA017553140226dlvsa25_1Plasma Healthy Former M
SA017554140228dlvsa32_1Plasma Healthy Former M
SA017555140226dlvsa32_1Plasma Healthy Former M
SA017556140225dlvsa38_1Plasma Healthy Former M
SA017557140227dlvsa27_1Plasma Healthy Former M
SA017558140227dlvsa05_1Plasma Healthy Former M
SA017559140227dlvsa38_1Plasma Healthy Former M
SA017560140225dlvsa11_1Plasma Healthy Former M
SA017561140225dlvsa29_1Plasma Healthy Former M
SA017562140226dlvsa38_1Plasma Healthy Former M
SA017563140225dlvsa47_1Plasma Healthy Former M
SA017564140228dlvsa41_1Plasma Healthy Former M
SA017565140227dlvsa12_1Plasma Healthy Former M
SA017566140226dlvsa01_1Plasma Healthy Former M
SA017587140225dlvsa43_1Serum Adenocarcinoma Current F
SA017588140228dlvsa07_1Serum Adenocarcinoma Current F
SA017589140227dlvsa46_1Serum Adenocarcinoma Current F
SA017590140228dlvsa38_1Serum Adenocarcinoma Current F
SA017591140226dlvsa35_1Serum Adenocarcinoma Current F
SA017592140228dlvsa29_1Serum Adenocarcinoma Current F
SA017593140226dlvsa29_1Serum Adenocarcinoma Current F
SA017594140228dlvsa16_1Serum Adenocarcinoma Current F
SA017595140227dlvsa35_1Serum Adenocarcinoma Current F
SA017596140226dlvsa40_1Serum Adenocarcinoma Current M
SA017597140227dlvsa13_1Serum Adenocarcinoma Current M
SA017598140228dlvsa27_1Serum Adenocarcinoma Current M
SA017599140225dlvsa13_1Serum Adenocarcinoma Current M
SA017600140226dlvsa20_1Serum Adenocarcinoma Current M
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Collection:

Collection ID:CO000400
Collection Summary:Blood samples (serum and plasma) were collected from NSCLC adenocarcinoma and control subjects with patient consent using approved IRB protocols (LC001 for cancer cases and LC002 for control cases).
Collection Protocol Filename:Cancer_Epidemiol_Biomarkers_Prev-2015-Fahrmann-1716-23.pdf
Sample Type:Blood

Treatment:

Treatment ID:TR000420
Treatment Summary:Subjects were recruited over a 4-year period (2010–2014) from the UC Davis Medical Center and Cancer Center Clinics. All subjects were diagnosed with NSCLC adenocarcinoma before specimen collection. The control population was heavily recruited from spouses and family members accompanying a lung cancer patient to their clinic to maintain as much of a similar environment and life styles, especially diet and smoking history, as possible. Cases were frequency matched with controls for gender, age, and smoking history. Only cases diagnosed with NSCLC adenocarcinoma were used in these studies. Fasting status was not controlled for as individuals were recruited upon their arrival to the clinic. The first set (ADC1) used for biomarker development consisted of serum and plasma samples obtained from 52 stages I–IV NSCLC adenocarcinoma patients (52 plasma and 49 serum), and 31 healthy controls (31 pairs of serum and plasma) for a total of 163 samples. This set was regarded as the training set for biomarker discovery and classifier development. A second, independent case–control study (ADC2) consisting of serum and plasma samples collected from 43 stage I–IV NSCLC adenocarcinoma patients and 43 healthy controls (total 172 samples) was used as an independent test set for biomarker evaluation.
Treatment Protocol Filename:Cancer_Epidemiol_Biomarkers_Prev-2015-Fahrmann-1716-23.pdf

Sample Preparation:

Sampleprep ID:SP000413
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 AN000620
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 GC-TOF
Ion Mode POSITIVE
Units peak area

Chromatography:

Chromatography ID:CH000445
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 (initial condition)
Column Temperature:50 - 330°C
Flow Rate:1 ml/min
Injection Temperature:50°C ramped to 250°C by 12°C/s
Sample Injection:0.5µl
Oven Temperature:50°C for 1 min, then ramped at 20°C/min to 330°C, held constant for 5 min
Transferline Temperature:230°C
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:MS000553
Analysis ID:AN000620
Instrument Name:Leco GC-TOF
Instrument Type:GC-TOF
MS Type:EI
Ion Mode:POSITIVE
Ion Source Temperature:250°C
Ionization Energy:70eV
Mass Accuracy:Nominal
Spray Voltage:250°C
Scan Range Moverz:85-500
Scanning Cycle:17 Hz
Skimmer Voltage:1850 V
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