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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
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.
Study ID | ST002764 |
Study 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 |
Study 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. Study |
Institute | Icahn School of Medicine at Mount Sinai |
Department | Environmental Medicine and Public Health |
Laboratory | Integrated Data Science Laboratory for Metabolomics and Exposomics |
Last Name | Barupal |
First Name | Dinesh |
Address | CAM Building 102street |
dinesh.barupal@mssm.edu | |
Phone | 5309794354 |
Submit Date | 2023-06-28 |
Raw Data Available | Yes |
Raw Data File Type(s) | mzML |
Analysis Type Detail | LC-MS |
Release Date | 2023-07-03 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
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 |
Species Group: | Mammals |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
mb_sample_id | local_sample_id | liver_cancer_outcome |
---|---|---|
SA291702 | BPL1415 0873 | Case |
SA291703 | BPL1415 0874 | Case |
SA291704 | BPL1415 0689 | Case |
SA291705 | BPL1415 0691 | Case |
SA291706 | BPL1415 0694 | Case |
SA291707 | BPL1415 0686 | Case |
SA291708 | BPL1415 0870 | Case |
SA291709 | BPL1415 0683 | Case |
SA291710 | BPL1415 0878 | Case |
SA291711 | BPL1415 0675 | Case |
SA291712 | BPL1415 0678 | Case |
SA291713 | BPL1415 0679 | Case |
SA291714 | BPL1415 0696 | Case |
SA291715 | BPL1415 0876 | Case |
SA291716 | BPL1415 0685 | Case |
SA291717 | BPL1415 0699 | Case |
SA291718 | BPL1415 0861 | Case |
SA291719 | BPL1415 0711 | Case |
SA291720 | BPL1415 0713 | Case |
SA291721 | BPL1415 0714 | Case |
SA291722 | BPL1415 0718 | Case |
SA291723 | BPL1415 0860 | Case |
SA291724 | BPL1415 0709 | Case |
SA291725 | BPL1415 0863 | Case |
SA291726 | BPL1415 0867 | Case |
SA291727 | BPL1415 0880 | Case |
SA291728 | BPL1415 0702 | Case |
SA291729 | BPL1415 0865 | Case |
SA291730 | BPL1415 0707 | Case |
SA291731 | BPL1415 0705 | Case |
SA291732 | BPL1415 0697 | Case |
SA291733 | BPL1415 0672 | Case |
SA291734 | BPL1415 0643 | Case |
SA291735 | BPL1415 0896 | Case |
SA291736 | BPL1415 0644 | Case |
SA291737 | BPL1415 0895 | Case |
SA291738 | BPL1415 0892 | Case |
SA291739 | BPL1415 0646 | Case |
SA291740 | BPL1415 0641 | Case |
SA291741 | BPL1415 0639 | Case |
SA291742 | BPL1415 0901 | Case |
SA291743 | BPL1415 0630 | Case |
SA291744 | BPL1415 0632 | Case |
SA291745 | BPL1415 0633 | Case |
SA291746 | BPL1415 0636 | Case |
SA291747 | BPL1415 0899 | Case |
SA291748 | BPL1415 0811 | Case |
SA291749 | BPL1415 0652 | Case |
SA291750 | BPL1415 0665 | Case |
SA291751 | BPL1415 0885 | Case |
SA291752 | BPL1415 0666 | Case |
SA291753 | BPL1415 0883 | Case |
SA291754 | BPL1415 0671 | Case |
SA291755 | BPL1415 0669 | Case |
SA291756 | BPL1415 0662 | Case |
SA291757 | BPL1415 0661 | Case |
SA291758 | BPL1415 0889 | Case |
SA291759 | BPL1415 0654 | Case |
SA291760 | BPL1415 0657 | Case |
SA291761 | BPL1415 0658 | Case |
SA291762 | BPL1415 0887 | Case |
SA291763 | BPL1415 0719 | Case |
SA291764 | BPL1415 0722 | Case |
SA291765 | BPL1415 0781 | Case |
SA291766 | BPL1415 0828 | Case |
SA291767 | BPL1415 0826 | Case |
SA291768 | BPL1415 0783 | Case |
SA291769 | BPL1415 0785 | Case |
SA291770 | BPL1415 0825 | Case |
SA291771 | BPL1415 0778 | Case |
SA291772 | BPL1415 0777 | Case |
SA291773 | BPL1415 0768 | Case |
SA291774 | BPL1415 0834 | Case |
SA291775 | BPL1415 0769 | Case |
SA291776 | BPL1415 0831 | Case |
SA291777 | BPL1415 0774 | Case |
SA291778 | BPL1415 0772 | Case |
SA291779 | BPL1415 0788 | Case |
SA291780 | BPL1415 0789 | Case |
SA291781 | BPL1415 0802 | Case |
SA291782 | BPL1415 0816 | Case |
SA291783 | BPL1415 0804 | Case |
SA291784 | BPL1415 0806 | Case |
SA291785 | BPL1415 0808 | Case |
SA291786 | BPL1415 0814 | Case |
SA291787 | BPL1415 0800 | Case |
SA291788 | BPL1415 0817 | Case |
SA291789 | BPL1415 0791 | Case |
SA291790 | BPL1415 0823 | Case |
SA291791 | BPL1415 0820 | Case |
SA291792 | BPL1415 0794 | Case |
SA291793 | BPL1415 0797 | Case |
SA291794 | BPL1415 0796 | Case |
SA291795 | BPL1415 0765 | Case |
SA291796 | BPL1415 0763 | Case |
SA291797 | BPL1415 0735 | Case |
SA291798 | BPL1415 0849 | Case |
SA291799 | BPL1415 0736 | Case |
SA291800 | BPL1415 0738 | Case |
SA291801 | BPL1415 0741 | Case |
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 -70C. |
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 |