Summary of Study ST000396

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 PR000309. The data can be accessed directly via it's Project DOI: 10.21228/M86G6V This work is supported by NIH grant, U2C- DK119886.

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Study IDST000396
Study TitleLung Cancer Plasma Discovery
Study SummaryRecently, major efforts have been directed toward early detection of lung cancer through low-dose computed tomography (LDCT) scanning. Data from the National Lung Screening Trial (NLST) suggest that yearly screening with thoracic LDCT scanning for high-risk current and former smokers reduces lung cancer mortality by 20% and total mortality by 7%. However, issues including indeterminate nodules detected by LDCT and radiation exposure impact the practicality of LDCT-based screening on a national and global basis. A blood-based biomarker or multiplexed marker panel that could complement LDCT would represent a major advance in implementing lung cancer screening. Efforts to develop blood-based biomarkers for lung cancer early detection using a variety of methodologies are currently ongoing. Proteomic studies have led to the identification of several candidate markers including pro-surfactantproteinB(pro-SFTPB), a target of a lineage-survival oncogene in lung cancer, NKX2-1.Validation studies using blood samples collected at the time of LDCT screening for lung cancer substantiated the performance of pro-SFTPB. Multivariable logistic regression models were used to evaluate the predictive ability of pro-SFTPB. The area under the curve (AUC) values of the full model with and without pro-SFTPB were 0.741 (95% CI, 0.696 to 0.783) and 0.669 (95%CI, 0.620 to 0.717), respectively (difference in AUC, P_.001). Single markers are unlikely to have sufficient performance for implementation in a screening setting, hence the need to explore several discovery platforms to identify markers that provide complementary performance. Metabolomics represents a global unbiased approach to the profiling of small molecules and has been established as a platform for biomarker discovery for a variety of human biofluids and tissues. Here we used an untargeted liquid chromatography/mass spectrometry (MS) metabolomics approach to identify metabolites that distinguish human sera collected before the diagnosis of lung cancer from matched control sera in a prospective cohort of highrisk patients from the Beta-Carotene and Retinol Efficacy Trial (CARET).
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 Date2016-05-10
Raw Data AvailableYes
Raw Data File Type(s)cdf
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/M86G6V
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000309
Project DOI:doi: 10.21228/M86G6V
Project Title:Lung Cancer Plasma Discovery
Project Summary:Recently, major efforts have been directed toward early detection of lung cancer through low-dose computed tomography (LDCT) scanning. Data from the National Lung Screening Trial (NLST) suggest that yearly screening with thoracic LDCT scanning for high-risk current and former smokers reduces lung cancer mortality by 20% and total mortality by 7%. However, issues including indeterminate nodules detected by LDCT and radiation exposure impact the practicality of LDCT-based screening on a national and global basis. A blood-based biomarker or multiplexed marker panel that could complement LDCT would represent a major advance in implementing lung cancer screening. Efforts to develop blood-based biomarkers for lung cancer early detection using a variety of methodologies are currently ongoing. Proteomic studies have led to the identification of several candidate markers including pro-surfactantproteinB(pro-SFTPB), a target of a lineage-survival oncogene in lung cancer, NKX2-1.Validation studies using blood samples collected at the time of LDCT screening for lung cancer substantiated the performance of pro-SFTPB. Multivariable logistic regression models were used to evaluate the predictive ability of pro-SFTPB. The area under the curve (AUC) values of the full model with and without pro-SFTPB were 0.741 (95% CI, 0.696 to 0.783) and 0.669 (95%CI, 0.620 to 0.717), respectively (difference in AUC, P_.001). Single markers are unlikely to have sufficient performance for implementation in a screening setting, hence the need to explore several discovery platforms to identify markers that provide complementary performance. Metabolomics represents a global unbiased approach to the profiling of small molecules and has been established as a platform for biomarker discovery for a variety of human biofluids and tissues. Here we used an untargeted liquid chromatography/mass spectrometry (MS) metabolomics approach to identify metabolites that distinguish human sera collected before the diagnosis of lung cancer from matched control sera in a prospective cohort of highrisk patients from the Beta-Carotene and Retinol Efficacy Trial (CARET).
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:SU000417
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Age Or Age Range:45-74
Gender:M/F
Human Smoking Status:Current vs. former
Species Group:Mammals

Factors:

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

mb_sample_id local_sample_id Age Group Sex Smoking Status Diagnosis
SA018857110630bwasa12_245-49 Male Current -
SA018858110702bwasa44_145-49 Male Current -
SA018856110702bwasa17_145-49 Male Current Adenocarcinoma
SA018781110630bwasa49_250-54 Female Current -
SA018782110701bwasa11_250-54 Female Current -
SA018784110703bwasa31_150-54 Female Current -
SA018787110704bwasa08_150-54 Female Current -
SA018788110702bwasa09_150-54 Female Current -
SA018789110701bwasa33_250-54 Female Current -
SA018790110701bwasa44_150-54 Female Current -
SA018791110705bwasa20_150-54 Female Current -
SA018792110704bwasa24_150-54 Female Current -
SA018793110629bwasa50_250-54 Female Current -
SA018988110701bwasa35_250-54 Female Current -
SA018989110704bwasa28_150-54 Female Current -
SA019051110701bwasa09_250-54 Female Current -
SA019052110703bwasa23_150-54 Female Current -
SA018785110703bwasa24_150-54 Female Current Adenocarcinoma
SA018795110702bwasa25_150-54 Female Current Adenocarcinoma
SA018987110702bwasa30_150-54 Female Current Adenocarcinoma
SA019050110629bwasa47_250-54 Female Current Adenocarcinoma
SA018783110702bwasa24_150-54 Female Current Other NSCLC
SA018794110703bwasa35_150-54 Female Current Other NSCLC
SA018786110701bwasa34_250-54 Female Current Squamous cell
SA018860110704bwasa31_150-54 Female Former -
SA018861110703bwasa43_150-54 Female Former -
SA018862110704bwasa25_150-54 Female Former -
SA018863110704bwasa49_150-54 Female Former -
SA018864110701bwasa23_250-54 Female Former Adenocarcinoma
SA018859110705bwasa16_150-54 Female Former Other NSCLC
SA018760110629bwasa37_250-54 Male Current -
SA018761110701bwasa17_250-54 Male Current -
SA018773110701bwasa25_250-54 Male Current -
SA018774110702bwasa18_150-54 Male Current -
SA018866110704bwasa30_150-54 Male Current -
SA018867110702bwasa16_150-54 Male Current -
SA018868110703bwasa32_150-54 Male Current -
SA018870110703bwasa01_150-54 Male Current -
SA019029110703bwasa42_150-54 Male Current -
SA019030110629bwasa34_250-54 Male Current -
SA019032110702bwasa48_150-54 Male Current -
SA019033110701bwasa43_150-54 Male Current -
SA019035110702bwasa42_150-54 Male Current -
SA019037110701bwasa13_250-54 Male Current -
SA018772110630bwasa29_250-54 Male Current Adenocarcinoma
SA019031110629bwasa42_250-54 Male Current Adenocarcinoma
SA019034110701bwasa15_250-54 Male Current Adenocarcinoma
SA019036110705bwasa29_150-54 Male Current Adenocarcinoma
SA018762110703bwasa16_150-54 Male Current Squamous cell
SA018865110704bwasa07_150-54 Male Current Squamous cell
SA018869110703bwasa30_150-54 Male Current Squamous cell
SA018991110702bwasa15_150-54 Male Former -
SA018992110630bwasa30_250-54 Male Former -
SA019038110630bwasa36_250-54 Male Former -
SA019040110701bwasa29_350-54 Male Former -
SA018990110703bwasa03_150-54 Male Former Other NSCLC
SA019039110630bwasa27_250-54 Male Former Squamous cell
SA018796110630bwasa16_255-59 Female Current -
SA018797110704bwasa27_155-59 Female Current -
SA018801110630bwasa04_255-59 Female Current -
SA018802110630bwasa26_255-59 Female Current -
SA018803110701bwasa42_155-59 Female Current -
SA018804110701bwasa27_355-59 Female Current -
SA018841110630bwasa31_255-59 Female Current -
SA018842110630bwasa45_255-59 Female Current -
SA018994110702bwasa40_155-59 Female Current -
SA018995110630bwasa32_255-59 Female Current -
SA018799110630bwasa01_255-59 Female Current Adenocarcinoma
SA018800110704bwasa35_155-59 Female Current Adenocarcinoma
SA018843110703bwasa48_155-59 Female Current Other NSCLC
SA018798110701bwasa39_255-59 Female Current Squamous cell
SA018993110703bwasa37_155-59 Female Current Squamous cell
SA018775110704bwasa21_155-59 Male Current -
SA018777110704bwasa34_155-59 Male Current -
SA018805110629bwasa32_255-59 Male Current -
SA018806110629bwasa44_255-59 Male Current -
SA018807110704bwasa38_155-59 Male Current -
SA018811110704bwasa37_155-59 Male Current -
SA018812110703bwasa29_155-59 Male Current -
SA018813110704bwasa39_155-59 Male Current -
SA018872110630bwasa14_255-59 Male Current -
SA018874110704bwasa42_155-59 Male Current -
SA018875110702bwasa02_155-59 Male Current -
SA018876110702bwasa13_155-59 Male Current -
SA018951110630bwasa39_255-59 Male Current -
SA018952110705bwasa15_155-59 Male Current -
SA018953110705bwasa10_255-59 Male Current -
SA018954110704bwasa43_155-59 Male Current -
SA018776110703bwasa44_155-59 Male Current Adenocarcinoma
SA018809110702bwasa12_155-59 Male Current Adenocarcinoma
SA018871110702bwasa38_155-59 Male Current Adenocarcinoma
SA018873110629bwasa36_255-59 Male Current Adenocarcinoma
SA018955110702bwasa46_155-59 Male Current Adenocarcinoma
SA018808110703bwasa05_155-59 Male Current Other NSCLC
SA018810110703bwasa15_155-59 Male Current Squamous cell
SA018956110704bwasa03_155-59 Male Current Squamous cell
SA018764110703bwasa13_155-59 Male Former -
SA018765110703bwasa07_155-59 Male Former -
SA018878110630bwasa34_255-59 Male Former -
SA018879110630bwasa11_555-59 Male Former -
Showing page 1 of 3     Results:    1  2  3  Next     Showing results 1 to 100 of 299

Collection:

Collection ID:CO000411
Collection Summary:In total, 208 patients with lung cancer were selected from 222 patients with non–small-cell lung cancer (NSCLC) with serum available in the CARET repository from blood draws that occurred up to 12 months before diagnosis. Fourteen patients with insufficient sample available for the study were excluded.Two control individuals who were free of lung cancer were matched to each patient case on age at baseline (5-year groups), sex, baseline smoking status (current v former), and study enrollment phase (pilot [1985 to 1988] or full-scale trial [1989 to 1994], thus accounting for sample storage time). For one patient, only a single control could be matched, resulting in a total of 208 patients and 415 controls included in the study. The samples were divided into two sets; samples from 100 matched sets were used for biomarker discovery (the discovery set), and the remaining 108 matched sets were reserved for validation of markers identified by the discovery efforts (the validation set). All CARET participants provided informed consent at recruitment and throughout follow-up, and the institutional review boards at each of the six study centers approved all study procedures.
Collection Protocol Filename:JCO-2015-Wikoff-3880-6.pdf
Sample Type:Blood
Blood Serum Or Plasma:Plasma

Treatment:

Treatment ID:TR000431
Treatment Summary:Potential confounders and effect modifiers on the DAS and lung cancer association were examined by the Mann-Whitney U test or Kruskal-Wallis test, stratified by case-control status, to assess association between DAS and several potential confounders, including sex, age, fasting time (hours since last meal), body mass index, smoking status (current v former), pack-years, and CARET exposure population (asbestos-exposed v heavy smoker cohort), as well as histology, stage of disease, and time of blood draw with respect to diagnosis (0 to 6 months v 6 to 12 months prior) among patients with lung cancer only.
Treatment Protocol Filename:JCO-2015-Wikoff-3880-6.pdf
Human Fasting:0-30 Hours

Sample Preparation:

Sampleprep ID:SP000424
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 AN000633
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:CH000458
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:MS000566
Analysis ID:AN000633
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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