Summary of Study ST002764

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 PR001722. The data can be accessed directly via it's Project DOI: 10.21228/M8441W 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 IDST002764
Study TitleIdentification of pre-diagnostic lipid sets associated with liver cancer risk using untargeted lipidomics and chemical set analysis – a nested case-control study within the ATBC cohort
Study SummaryIn pre-disposed individuals, a reprogramming of the hepatic lipid metabolism may support liver cancer initiation. We conducted a high-resolution mass spectrometry based untargeted lipidomics analysis of pre-diagnostic serum samples from a nested case-control study (219 liver cancer cases and 219 controls) within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Out of 462 annotated lipids, 158 (34.2%) were associated with liver cancer risk in a conditional logistic regression analysis at a false discovery rate (FDR) < 0.05. A chemical set enrichment analysis (ChemRICH) and co-regulatory set analysis suggested that 22/28 lipid classes and 47/83 correlation modules were significantly associated with liver cancer risk (FDR <0.05). Strong positive associations were observed for monounsaturated fatty acids (MUFA), triacylglycerols (TAGs), and phosphatidylcholines (PCs) having MUFA acyl chains. Negative associations were observed for sphingolipids (ceramides and sphingomyelins), lysophosphatidylcholines, cholesterol esters and polyunsaturated fatty acids (PUFA) containing TAGs and PCs. Stearoyl-CoA desaturase enzyme 1 (SCD1), a rate limiting enzyme in fatty acid metabolism and ceramidases seems to be critical in this reprogramming. In conclusion, our study reports pre-diagnostic lipid changes that provide novel insights into hepatic lipid metabolism reprogramming may contribute to a pro-cell growth and anti-apoptotic tissue environment and, in turn, support liver cancer initiation. Study
Institute
Icahn School of Medicine at Mount Sinai
DepartmentEnvironmental Medicine and Public Health
LaboratoryIntegrated Data Science Laboratory for Metabolomics and Exposomics
Last NameBarupal
First NameDinesh
AddressCAM Building 102street
Emaildinesh.barupal@mssm.edu
Phone5309794354
Submit Date2023-06-28
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2023-07-03
Release Version1
Dinesh Barupal Dinesh Barupal
https://dx.doi.org/10.21228/M8441W
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001722
Project DOI:doi: 10.21228/M8441W
Project Title:Identification of pre-diagnostic lipid sets associated with liver cancer risk using untargeted lipidomics and chemical set analysis – a nested case-control study within the ATBC cohort
Project Summary:In pre-disposed individuals, a reprogramming of the hepatic lipid metabolism may support liver cancer initiation. We conducted a high-resolution mass spectrometry based untargeted lipidomics analysis of pre-diagnostic serum samples from a nested case-control study (219 liver cancer cases and 219 controls) within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Out of 462 annotated lipids, 158 (34.2%) were associated with liver cancer risk in a conditional logistic regression analysis at a false discovery rate (FDR) < 0.05. A chemical set enrichment analysis (ChemRICH) and co-regulatory set analysis suggested that 22/28 lipid classes and 47/83 correlation modules were significantly associated with liver cancer risk (FDR <0.05). Strong positive associations were observed for monounsaturated fatty acids (MUFA), triacylglycerols (TAGs), and phosphatidylcholines (PCs) having MUFA acyl chains. Negative associations were observed for sphingolipids (ceramides and sphingomyelins), lysophosphatidylcholines, cholesterol esters and polyunsaturated fatty acids (PUFA) containing TAGs and PCs. Stearoyl-CoA desaturase enzyme 1 (SCD1), a rate limiting enzyme in fatty acid metabolism and ceramidases seems to be critical in this reprogramming. In conclusion, our study reports pre-diagnostic lipid changes that provide novel insights into hepatic lipid metabolism reprogramming may contribute to a pro-cell growth and anti-apoptotic tissue environment and, in turn, support liver cancer initiation.
Institute:Icahn School of Medicine at Mount Sinai
Last Name:Barupal
First Name:Dinesh
Address:CAM Building 102E street
Email:dinesh.barupal@mssm.edu
Phone:5309794354
Contributors:Dinesh K. Barupal, Mark L. Ramos, Andrea A. Florio, William A. Wheeler, Stephanie J. Weinstein, Demetrius Albanes, Oliver Fiehn, Barry I. Graubard, Jessica L. Petrick, Katherine A. McGlynn

Subject:

Subject ID:SU002871
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

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

mb_sample_id local_sample_id liver_cancer_outcome
SA291702BPL1415 0873Case
SA291703BPL1415 0874Case
SA291704BPL1415 0689Case
SA291705BPL1415 0691Case
SA291706BPL1415 0694Case
SA291707BPL1415 0686Case
SA291708BPL1415 0870Case
SA291709BPL1415 0683Case
SA291710BPL1415 0878Case
SA291711BPL1415 0675Case
SA291712BPL1415 0678Case
SA291713BPL1415 0679Case
SA291714BPL1415 0696Case
SA291715BPL1415 0876Case
SA291716BPL1415 0685Case
SA291717BPL1415 0699Case
SA291718BPL1415 0861Case
SA291719BPL1415 0711Case
SA291720BPL1415 0713Case
SA291721BPL1415 0714Case
SA291722BPL1415 0718Case
SA291723BPL1415 0860Case
SA291724BPL1415 0709Case
SA291725BPL1415 0863Case
SA291726BPL1415 0867Case
SA291727BPL1415 0880Case
SA291728BPL1415 0702Case
SA291729BPL1415 0865Case
SA291730BPL1415 0707Case
SA291731BPL1415 0705Case
SA291732BPL1415 0697Case
SA291733BPL1415 0672Case
SA291734BPL1415 0643Case
SA291735BPL1415 0896Case
SA291736BPL1415 0644Case
SA291737BPL1415 0895Case
SA291738BPL1415 0892Case
SA291739BPL1415 0646Case
SA291740BPL1415 0641Case
SA291741BPL1415 0639Case
SA291742BPL1415 0901Case
SA291743BPL1415 0630Case
SA291744BPL1415 0632Case
SA291745BPL1415 0633Case
SA291746BPL1415 0636Case
SA291747BPL1415 0899Case
SA291748BPL1415 0811Case
SA291749BPL1415 0652Case
SA291750BPL1415 0665Case
SA291751BPL1415 0885Case
SA291752BPL1415 0666Case
SA291753BPL1415 0883Case
SA291754BPL1415 0671Case
SA291755BPL1415 0669Case
SA291756BPL1415 0662Case
SA291757BPL1415 0661Case
SA291758BPL1415 0889Case
SA291759BPL1415 0654Case
SA291760BPL1415 0657Case
SA291761BPL1415 0658Case
SA291762BPL1415 0887Case
SA291763BPL1415 0719Case
SA291764BPL1415 0722Case
SA291765BPL1415 0781Case
SA291766BPL1415 0828Case
SA291767BPL1415 0826Case
SA291768BPL1415 0783Case
SA291769BPL1415 0785Case
SA291770BPL1415 0825Case
SA291771BPL1415 0778Case
SA291772BPL1415 0777Case
SA291773BPL1415 0768Case
SA291774BPL1415 0834Case
SA291775BPL1415 0769Case
SA291776BPL1415 0831Case
SA291777BPL1415 0774Case
SA291778BPL1415 0772Case
SA291779BPL1415 0788Case
SA291780BPL1415 0789Case
SA291781BPL1415 0802Case
SA291782BPL1415 0816Case
SA291783BPL1415 0804Case
SA291784BPL1415 0806Case
SA291785BPL1415 0808Case
SA291786BPL1415 0814Case
SA291787BPL1415 0800Case
SA291788BPL1415 0817Case
SA291789BPL1415 0791Case
SA291790BPL1415 0823Case
SA291791BPL1415 0820Case
SA291792BPL1415 0794Case
SA291793BPL1415 0797Case
SA291794BPL1415 0796Case
SA291795BPL1415 0765Case
SA291796BPL1415 0763Case
SA291797BPL1415 0735Case
SA291798BPL1415 0849Case
SA291799BPL1415 0736Case
SA291800BPL1415 0738Case
SA291801BPL1415 0741Case
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Collection:

Collection ID:CO002864
Collection Summary:Baseline visit blood samples were collected from ATBC participants after an overnight fast (usually at least 12 hours). Blood samples were centrifuged and serum was aliquoted and stored at -70C.
Sample Type:Blood (serum)

Treatment:

Treatment ID:TR002880
Treatment Summary:This is an nested case control study within the ATBC cohort. There were not treatment groups.

Sample Preparation:

Sampleprep ID:SP002877
Sampleprep Summary:The lipidome analysis was performed at the West Coast Metabolomics Center (University of California Davis Genome Center), using 50μL of serum as previously described in https://www.nature.com/articles/sdata2018263

Combined analysis:

Analysis ID AN004498 AN004499
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Agilent 1290 Infinity Agilent 1290 Infinity
Column Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um)
MS Type ESI ESI
MS instrument type QTOF QTOF
MS instrument name Agilent 6550 QTOF Agilent 6530 QTOF
Ion Mode NEGATIVE POSITIVE
Units normalized peak intensity normalized peak intensity

Chromatography:

Chromatography ID:CH003380
Chromatography Summary:The LC/QTOFMS analyses are performed using an Agilent 1290 Infinity LC system (G4220A binary pump, G4226A autosampler, and G1316C Column Thermostat) coupled to either an Agilent 6530 (positive ion mode) or an Agilent 6550 mass spectrometer equipped with an ion funnel (iFunnel) (negative ion mode). Lipids are separated on an Acquity UPLC CSH C18 column (100 x 2.1 mm; 1.7 µm) maintained at 65°C at a flow-rate of 0.6 mL/min. Solvent pre-heating (Agilent G1316) was used. The mobile phases consist of 60:40 acetonitrile:water with 10 mM ammonium formate and 0.1% formic acid (A) and 90:10 propan-2-ol:acetonitrile with 10 mM ammonium formate and 0.1% formic acid. The gradient is as follows: 0 min 85% (A); 0–2 min 70% (A); 2–2.5 min 52% (A); 2.5–11 min 18% (A); 11–11.5 min 1% (A); 11.5–12 min 1% (A); 12–12.1 min 85% (A); 12.1–15 min 85% (A). A sample volume of 3 µL is used for the injection. Sample temperature is maintained at 4°C in the autosampler.
Instrument Name:Agilent 1290 Infinity
Column Name:Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um)
Column Temperature:65
Flow Gradient:0 min 85% (A); 0-2 min 70% (A); 2-2.5 min 52% (A); 2.5-11 min 18% (A); 11-11.5 min 1% (A); 11.5-12 min 1% (A); 12-12.1 min 85% (A); 12.1-15 min 85% (A).
Flow Rate:0.6
Solvent A:60% acetonitrile/40% water; 0.1% formic acid; 10 mM ammonium formate
Solvent B:90% isopropanol/10% acetonitrile; 0.1% formic acid; 10 mM ammonium formate
Chromatography Type:Reversed phase

MS:

MS ID:MS004245
Analysis ID:AN004498
Instrument Name:Agilent 6550 QTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:The quadrupole/time-of-flight (QTOF) mass spectrometers are operated with electrospray ionization (ESI) performing full scan in the mass range m/z 65–1700 in positive (Agilent 6530, equipped with a JetStreamSource) and negative (Agilent 6550, equipped with a dual JetStream Source) modes producing both unique and complementary spectra. Instrument parameters are as follows (positive mode) Gas Temp 325°C, Gas Flow 8 l/min, Nebulizer 35 psig, Sheath Gas 350°C, Sheath Gas Flow 11, Capillary Voltage 3500 V, Nozzle Voltage 1000V, Fragmentor 120V, Skimmer 65V. Data (both profile and centroid) are collected at a rate of 2 scans per second. In negative ion mode, Gas Temp 200°C, Gas Flow 14 l/min, Fragmentor 175V, with the other parameters identical to positive ion mode. For the 6530 QTOF, a reference solution generating ions of 121.050 and 922.007 m/z in positive mode and 119.036 and 966.0007 m/z in negative mode, and these are used for continuous mass correction. For the 6550, the reference solution is introduced via a dual spray ESI, with the same ions and continuous mass correction. Samples are injected (1.7 μl in positive mode and 5 μl in negative ion mode) with a needle wash for 20 seconds (wash solvent is isopropanol). The valve is switched back and forth during the run for washing; this has been shown to be essential for reducing carryover of less polar lipids.
Ion Mode:NEGATIVE
  
MS ID:MS004246
Analysis ID:AN004499
Instrument Name:Agilent 6530 QTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:The quadrupole/time-of-flight (QTOF) mass spectrometers are operated with electrospray ionization (ESI) performing full scan in the mass range m/z 65–1700 in positive (Agilent 6530, equipped with a JetStreamSource) and negative (Agilent 6550, equipped with a dual JetStream Source) modes producing both unique and complementary spectra. Instrument parameters are as follows (positive mode) Gas Temp 325°C, Gas Flow 8 l/min, Nebulizer 35 psig, Sheath Gas 350°C, Sheath Gas Flow 11, Capillary Voltage 3500 V, Nozzle Voltage 1000V, Fragmentor 120V, Skimmer 65V. Data (both profile and centroid) are collected at a rate of 2 scans per second. In negative ion mode, Gas Temp 200°C, Gas Flow 14 l/min, Fragmentor 175V, with the other parameters identical to positive ion mode. For the 6530 QTOF, a reference solution generating ions of 121.050 and 922.007 m/z in positive mode and 119.036 and 966.0007 m/z in negative mode, and these are used for continuous mass correction. For the 6550, the reference solution is introduced via a dual spray ESI, with the same ions and continuous mass correction. Samples are injected (1.7 μl in positive mode and 5 μl in negative ion mode) with a needle wash for 20 seconds (wash solvent is isopropanol). The valve is switched back and forth during the run for washing; this has been shown to be essential for reducing carryover of less polar lipids.
Ion Mode:POSITIVE
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