Summary of Study ST000390
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 PR000305. The data can be accessed directly via it's Project DOI: 10.21228/M8PG66 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 | ST000390 |
| Study Title | Metabolomic markers of altered nucleotide metabolism in early stage adenocarcinoma (part I) |
| Study Summary | Lung cancer has been the leading cause of cancer death in the United States and worldwide for many decades. Low dose spiral computerized tomography (LDCT) is likely to become the first approved screening and early detection test in the upcoming year, but it is plagued by a high false-positive rate. There is a need to develop complementary screening and early detection tools. A blood-based lung cancer signature is an attractive solution. Given that our knowledge of the molecular biology of smoking-induced lung cancer has dramatically increased over the past few years, this approach is plausible. To date, this effort has been focused on the identification of genomic and proteomic signatures with limited success. A broader strategy that incorporates additional cancer traits is needed. It is well recognized that wide coverage of cellular metabolism in cancer could help provide valuable diagnostic biomarkers and potentially identify molecular drivers of tumorigenesis. Recent advances in mass spectrometry have enabled comprehensive metabolomic analyses of lipids, carbohydrates, amino acids, and nucleotides within a variety of biologic matrices. Early evidence from metabolomic investigation of cancer has identified many altered biochemical profiles. However, to date, there have been few investigations of lung cancer, and most studies have looked at blood plasma or were limited by small sample sizes with mixed histologies. In the current investigation, gas chromatography time-offlight mass spectrometry (GC-TOF) was used to measure 462 lipid, carbohydrate, amino acid, organic acid, and nucleotide metabolites in 39 malignant and nonmalignant lung tissue pairs from current or former smokers with early stage adenocarcinoma. This study cohort represents patient characteristics and tumor histology most likely to be detected with LDCT screening. We hypothesize that identification of cancer-induced cellular and tissue level biochemical changes can offer a robust method for identification of candidate circulating biomarkers and improve our understanding of biochemical changes involved in adenocarcinoma tumorigenesis. |
| 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 |
| ofiehn@ucdavis.edu | |
| Phone | (530) 754-8258 |
| Submit Date | 2016-05-06 |
| Publications | doi: 10.1158/1940-6207 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | peg |
| Analysis Type Detail | GC-MS |
| Release Date | 2016-06-18 |
| Release Version | 2 |
| Release Comments | Updated study design factors |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR000305 |
| Project DOI: | doi: 10.21228/M8PG66 |
| Project Title: | Metabolomic markers of altered nucleotide metabolism in early stage adenocarcinoma |
| Project Summary: | Lung cancer has been the leading cause of cancer death in the United States and worldwide for many decades. Low dose spiral computerized tomography (LDCT) is likely to become the first approved screening and early detection test in the upcoming year, but it is plagued by a high false-positive rate. There is a need to develop complementary screening and early detection tools. A blood-based lung cancer signature is an attractive solution. Given that our knowledge of the molecular biology of smoking-induced lung cancer has dramatically increased over the past few years, this approach is plausible. To date, this effort has been focused on the identification of genomic and proteomic signatures with limited success. A broader strategy that incorporates additional cancer traits is needed. It is well recognized that wide coverage of cellular metabolism in cancer could help provide valuable diagnostic biomarkers and potentially identify molecular drivers of tumorigenesis. Recent advances in mass spectrometry have enabled comprehensive metabolomic analyses of lipids, carbohydrates, amino acids, and nucleotides within a variety of biologic matrices. Early evidence from metabolomic investigation of cancer has identified many altered biochemical profiles. However, to date, there have been few investigations of lung cancer, and most studies have looked at blood plasma or were limited by small sample sizes with mixed histologies. In the current investigation, gas chromatography time-offlight mass spectrometry (GC-TOF) was used to measure 462 lipid, carbohydrate, amino acid, organic acid, and nucleotide metabolites in 39 malignant and nonmalignant lung tissue pairs from current or former smokers with early stage adenocarcinoma. This study cohort represents patient characteristics and tumor histology most likely to be detected with LDCT screening. We hypothesize that identification of cancer-induced cellular and tissue level biochemical changes can offer a robust method for identification of candidate circulating biomarkers and improve our understanding of biochemical changes involved in adenocarcinoma tumorigenesis. |
| 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: 10.1158/1940-6207 |
Subject:
| Subject ID: | SU000411 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
| Age Or Age Range: | 55-91 |
| Gender: | M/F |
| Human Race: | Caucasian, Asian |
| 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 | Sex | Smoking Status | Diagnosis | Tumor Present |
|---|---|---|---|---|---|
| SA018330 | 121129bbdsa05_1 | F | Current Smoker | adenocarcinoma | No |
| SA018331 | 121129bbdsa33_1 | F | Current Smoker | adenocarcinoma | Yes |
| SA018328 | 121130bbdsa17_1 | F | Current Smoker | adenocarcinoma w/ BAC | No |
| SA018329 | 121130bbdsa21_1 | F | Current Smoker | adenocarcinoma w/ BAC | Yes |
| SA018356 | 121130bbdsa27_1 | F | Ex-Smoker | adenocarcinoma, multiple primaries | No |
| SA018357 | 121129bbdsa12_1 | F | Ex-Smoker | adenocarcinoma, multiple primaries | No |
| SA018358 | 121129bbdsa24_1 | F | Ex-Smoker | adenocarcinoma, multiple primaries | Yes |
| SA018359 | 121130bbdsa07_1 | F | Ex-Smoker | adenocarcinoma, multiple primaries | Yes |
| SA018360 | 121129bbdsa50_1 | F | Ex-Smoker | adenocarcinoma | No |
| SA018361 | 121129bbdsa34_1 | F | Ex-Smoker | adenocarcinoma | No |
| SA018362 | 121129bbdsa10_1 | F | Ex-Smoker | adenocarcinoma | No |
| SA018363 | 121130bbdsa12_1 | F | Ex-Smoker | adenocarcinoma | No |
| SA018364 | 121129bbdsa22_1 | F | Ex-Smoker | adenocarcinoma | No |
| SA018365 | 121130bbdsa05_1 | F | Ex-Smoker | adenocarcinoma | No |
| SA018366 | 121130bbdsa34_1 | F | Ex-Smoker | adenocarcinoma | No |
| SA018367 | 121129bbdsa17_1 | F | Ex-Smoker | adenocarcinoma | No |
| SA018336 | 121129bbdsa41_1 | F | Ex-Smoker | Adenocarcinoma | No |
| SA018368 | 121130bbdsa20_1 | F | Ex-Smoker | adenocarcinoma | Yes |
| SA018369 | 121129bbdsa13_1 | F | Ex-Smoker | adenocarcinoma | Yes |
| SA018370 | 121129bbdsa15_1 | F | Ex-Smoker | adenocarcinoma | Yes |
| SA018371 | 121130bbdsa09_1 | F | Ex-Smoker | adenocarcinoma | Yes |
| SA018372 | 121130bbdsa14_1 | F | Ex-Smoker | adenocarcinoma | Yes |
| SA018373 | 121130bbdsa01_1 | F | Ex-Smoker | adenocarcinoma | Yes |
| SA018374 | 121130bbdsa16_1 | F | Ex-Smoker | adenocarcinoma | Yes |
| SA018375 | 121130bbdsa06_1 | F | Ex-Smoker | adenocarcinoma | Yes |
| SA018337 | 121129bbdsa32_1 | F | Ex-Smoker | Adenocarcinoma | Yes |
| SA018350 | 121129bbdsa27_1 | F | Ex-Smoker | adenocarcinoma w/ bac | No |
| SA018338 | 121129bbdsa43_1 | F | Ex-Smoker | adenocarcinoma w/ BAC | No |
| SA018339 | 121130bbdsa11_1 | F | Ex-Smoker | adenocarcinoma w/ BAC | No |
| SA018340 | 121129bbdsa08_1 | F | Ex-Smoker | adenocarcinoma w/ BAC | No |
| SA018341 | 121129bbdsa26_1 | F | Ex-Smoker | adenocarcinoma w/ BAC | No |
| SA018342 | 121129bbdsa23_1 | F | Ex-Smoker | adenocarcinoma w/ BAC | No |
| SA018343 | 121129bbdsa06_1 | F | Ex-Smoker | adenocarcinoma w/ BAC | No |
| SA018352 | 121130bbdsa02_1 | F | Ex-Smoker | adenocarcinoma w/BAC | No |
| SA018353 | 121129bbdsa37_1 | F | Ex-Smoker | adenocarcinoma w/BAC | No |
| SA018332 | 121129bbdsa21_1 | F | Ex-Smoker | Adenocarcinoma w/ BAC | No |
| SA018333 | 121130bbdsa25_1 | F | Ex-Smoker | Adenocarcinoma w/ BAC | No |
| SA018351 | 121129bbdsa31_1 | F | Ex-Smoker | adenocarcinoma w/ bac | Yes |
| SA018344 | 121129bbdsa04_1 | F | Ex-Smoker | adenocarcinoma w/ BAC | Yes |
| SA018345 | 121130bbdsa35_1 | F | Ex-Smoker | adenocarcinoma w/ BAC | Yes |
| SA018346 | 121129bbdsa25_1 | F | Ex-Smoker | adenocarcinoma w/ BAC | Yes |
| SA018347 | 121130bbdsa03_1 | F | Ex-Smoker | adenocarcinoma w/ BAC | Yes |
| SA018348 | 121129bbdsa02_1 | F | Ex-Smoker | adenocarcinoma w/ BAC | Yes |
| SA018349 | 121129bbdsa44_1 | F | Ex-Smoker | adenocarcinoma w/ BAC | Yes |
| SA018354 | 121129bbdsa16_1 | F | Ex-Smoker | adenocarcinoma w/BAC | Yes |
| SA018355 | 121130bbdsa24_1 | F | Ex-Smoker | adenocarcinoma w/BAC | Yes |
| SA018334 | 121130bbdsa29_1 | F | Ex-Smoker | Adenocarcinoma w/ BAC | Yes |
| SA018335 | 121130bbdsa04_1 | F | Ex-Smoker | Adenocarcinoma w/ BAC | Yes |
| SA018378 | 121130bbdsa19_1 | M | Current Smoker | adenocarcinoma | No |
| SA018379 | 121129bbdsa48_1 | M | Current Smoker | adenocarcinoma | No |
| SA018380 | 121129bbdsa46_1 | M | Current Smoker | adenocarcinoma | Yes |
| SA018381 | 121130bbdsa23_1 | M | Current Smoker | adenocarcinoma | Yes |
| SA018376 | 121129bbdsa39_1 | M | Current Smoker | adenocarcinoma w/ BAC | No |
| SA018377 | 121130bbdsa08_1 | M | Current Smoker | adenocarcinoma w/ BAC | Yes |
| SA018400 | 121129bbdsa47_1 | M | Ex-Smoker | adenocarcinoma | No |
| SA018401 | 121130bbdsa31_1 | M | Ex-Smoker | adenocarcinoma | No |
| SA018402 | 121130bbdsa22_1 | M | Ex-Smoker | adenocarcinoma | No |
| SA018382 | 121129bbdsa38_1 | M | Ex-Smoker | Adenocarcinoma | No |
| SA018403 | 121129bbdsa40_1 | M | Ex-Smoker | adenocarcinoma | Yes |
| SA018404 | 121130bbdsa36_1 | M | Ex-Smoker | adenocarcinoma | Yes |
| SA018405 | 121129bbdsa11_1 | M | Ex-Smoker | adenocarcinoma | Yes |
| SA018383 | 121130bbdsa13_1 | M | Ex-Smoker | Adenocarcinoma | Yes |
| SA018384 | 121129bbdsa01_1 | M | Ex-Smoker | adenocarcinoma w/ BAC | No |
| SA018385 | 121129bbdsa45_1 | M | Ex-Smoker | adenocarcinoma w/ BAC | No |
| SA018386 | 121130bbdsa10_1 | M | Ex-Smoker | adenocarcinoma w/ BAC | No |
| SA018387 | 121129bbdsa14_1 | M | Ex-Smoker | adenocarcinoma w/ BAC | No |
| SA018388 | 121130bbdsa37_1 | M | Ex-Smoker | adenocarcinoma w/ BAC | No |
| SA018389 | 121129bbdsa09_1 | M | Ex-Smoker | adenocarcinoma w/ BAC | No |
| SA018390 | 121129bbdsa18_1 | M | Ex-Smoker | adenocarcinoma w/ BAC | No |
| SA018391 | 121129bbdsa35_1 | M | Ex-Smoker | adenocarcinoma w/ BAC | No |
| SA018392 | 121129bbdsa30_1 | M | Ex-Smoker | adenocarcinoma w/ BAC | Yes |
| SA018393 | 121129bbdsa29_1 | M | Ex-Smoker | adenocarcinoma w/ BAC | Yes |
| SA018394 | 121130bbdsa30_1 | M | Ex-Smoker | adenocarcinoma w/ BAC | Yes |
| SA018395 | 121130bbdsa15_1 | M | Ex-Smoker | adenocarcinoma w/ BAC | Yes |
| SA018396 | 121129bbdsa07_1 | M | Ex-Smoker | adenocarcinoma w/ BAC | Yes |
| SA018397 | 121130bbdsa26_1 | M | Ex-Smoker | adenocarcinoma w/ BAC | Yes |
| SA018398 | 121130bbdsa18_1 | M | Ex-Smoker | adenocarcinoma w/ BAC | Yes |
| SA018399 | 121130bbdsa32_1 | M | Ex-Smoker | adenocarcinoma w/ BAC | Yes |
| SA018319 | 121130bbdsa33_1 | - | - | - | - |
| SA018320 | 121129bbdsa19_1 | - | - | - | - |
| SA018321 | 121130bbdsa28_1 | - | - | - | - |
| SA018322 | 121129bbdsa49_1 | - | - | - | - |
| SA018323 | 121129bbdsa03_1 | - | - | - | - |
| SA018324 | 121129bbdsa20_1 | - | - | - | - |
| SA018325 | 121129bbdsa42_1 | - | - | - | - |
| SA018326 | 121129bbdsa28_1 | - | - | - | - |
| SA018327 | 121129bbdsa36_1 | - | - | - | - |
| Showing results 1 to 87 of 87 |
Collection:
| Collection ID: | CO000405 |
| Collection Summary: | Deidentified malignant and adjacent nonmalignant lung tissue was obtained from the New York University biorepository. Residual tumor and adjacent nonmalignant tissue was harvested from the resected lung after routine pathologic protocols were completed, following an approved Institutional Review Board (IRB) protocol with patient consent. Two to three tissue pieces were aliquoted into 1.5 mL Nunc vials, and then immediately placed in liquid nitrogen. After transport in liquid nitrogen, each vial was barcoded and stored at 80 C until analyzed. |
| Collection Protocol Filename: | Cancer_Prev_Res-2015-Wikoff-410-8.pdf |
| Sample Type: | Tissue |
Treatment:
| Treatment ID: | TR000425 |
| Treatment Summary: | All specimens were clinically annotated for age, gender, race, histology, smoking status, pack-years, and stage of disease. For this clinical study, samples were selected that came from patients who met the following criteria: (i) current or former smokers, (ii) adenocarcinoma histology, (iii) pathologic stage IA or IB, and (iv) had understood and signed the IRB consent form. |
| Treatment Protocol Filename: | Cancer_Prev_Res-2015-Wikoff-410-8.pdf |
Sample Preparation:
| Sampleprep ID: | SP000418 |
| 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 | AN000626 |
|---|---|
| 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 Pegasus III GC TOF |
| Ion Mode | POSITIVE |
| Units | counts |
Chromatography:
| Chromatography ID: | CH000451 |
| 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 |
| 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: | MS000559 |
| Analysis ID: | AN000626 |
| Instrument Name: | Leco Pegasus III GC TOF |
| Instrument Type: | GC-TOF |
| MS Type: | EI |
| Ion Mode: | POSITIVE |
| Ion Source Temperature: | 250 C |
| Ionization: | Pos |
| 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 |
