Summary of Study ST004166

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 PR002626. The data can be accessed directly via it's Project DOI: 10.21228/M86R9R 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 IDST004166
Study TitleDistinct skeletal muscle metabolomic alterations are associated with physical function, weight loss, and muscle mass in men with cancer
Study SummaryWe enrolled patients planning elective laparotomy for gastrointestinal or genitourinary cancer. Handgrip strength (HGS), stair climb power (SCP), and fasting plasma were collected within two weeks prior to surgery; rectus abdominis samples were obtained during surgery. Metabolomic perturbations associated with physical function (HGS, SCP), muscularity (lumbar cross-sectional area “CSA” from opportunistic CT), or weight loss (>5% over previous six months) were examined in plasma and muscle. The Mann-Whitney U-test compared metabolite abundance between weight-losing and weight-stable patients while Spearman’s correlation tested associations of abundance with CSA, HGS, or SCP. The “Globaltest” method assessed pathway alterations with weight loss, CSA, HGS, or SCP; the Benjamini-Hochberg adjustment was used to control for false discovery. Results: Patients (N=72) were male, median age 65 [interquartile range: 59-70], with 57% genitourinary cancer. Plasma and skeletal muscle metabolomic data were collected (N=64 and N=68, respectively). Weight loss was associated with significantly altered microbial, amino acid/derivative, fatty acid/lipid, and caffeine-related metabolism pathways in plasma (adjusted P<0.1). Lower CSA was associated with significantly altered fatty acid/lipid, galactose, glycerophospholipid, and histidine metabolism and bile secretion pathways in skeletal muscle (adjusted P<0.1). Worse HGS was nominally associated with altered plasma branched chain amino acid biosynthesis and altered skeletal muscle glutathione metabolism (unadjusted P≤0.05), while worse SCP was nominally associated with altered skeletal muscle amino sugar/nucleotide sugar metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis (unadjusted P≤0.05). Conclusions: Significant metabolomic alterations in plasma and skeletal muscle characterized cancer-related weight loss and reduced CSA, respectively. Nominal, function-specific alterations were detected with worse HGS and SCP which were distinct from those associated with weight loss or low CSA. Future larger studies may further characterize metabolomic profiles related to various functional outcomes and guide development of therapeutic targets to improve functional performance.
Institute
VA Puget Sound Health Care System
Last NameAnderson
First NameLindsey
Address1660 S. Columbian Way (S-182-GRECC), Seattle, WA, 98108, USA
Emaillindsey.anderson5@va.gov
Phone206-277-6719
Submit Date2025-09-02
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2025-09-25
Release Version1
Lindsey Anderson Lindsey Anderson
https://dx.doi.org/10.21228/M86R9R
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR002626
Project DOI:doi: 10.21228/M86R9R
Project Title:Distinct skeletal muscle metabolomic alterations are associated with physical function, weight loss, and muscle mass in men with cancer
Project Summary:Treatments for cancer cachexia, defined as involuntary weight and muscle mass loss leading to significant functional impairment, remain unavailable partly due to insufficient improvement of clinically meaningful outcomes in current trials. By reflecting downstream effects of cellular function, metabolomics may identify mechanisms contributing to poor functional performance. Previous metabolomic studies in cancer cachexia have identified alterations in amino acid metabolism with weight loss or low muscularity; none have examined perturbations with poor physical function. We hypothesized that distinct metabolic signals in plasma and muscle are associated with weight loss, low muscle mass, and impaired function in cancer cachexia. Our studies find that significant metabolomic alterations in plasma and skeletal muscle characterized cancer-related weight loss and reduced CSA, respectively. Nominal, function-specific alterations were detected with worse HGS and SCP which were distinct from those associated with weight loss or low CSA. Future larger studies may further characterize metabolomic profiles related to various functional outcomes and guide development of therapeutic targets to improve functional performance.
Institute:VA Puget Sound Health Care System
Last Name:Anderson
First Name:Lindsey
Address:1660 S. Columbian Way (S-182-GRECC), Seattle, WA, 98108, USA
Email:lindsey.anderson5@va.gov
Phone:206-277-6719

Subject:

Subject ID:SU004317
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Age Or Age Range:median (interquartile range): 65.0 (59.0, 70.0) years
Weight Or Weight Range:median (interquartile range): 88.3 (78.1, 106.7) kg
Height Or Height Range:median (interquartile range): 177.8 (172.7, 182.9) cm
Gender:Male
Human Inclusion Criteria:Males with histologically, cytologically, or image-based documented gastrointestinal or genitourinary cancer planning elective laparotomy were recruited from oncology or urology clinics at Veterans Affairs Puget Sound Health Care System in Seattle, WA, USA.
Human Exclusion Criteria:Participants were excluded for other conditions associated with cachexia (e.g., congestive heart failure, liver disease [aspartate aminotransferase or alanine aminotransferase equal or more than 3x normal levels], renal failure [creatinine equal or more than 2.5 mg/dL]), active infection, uncontrolled diabetes mellitus (HbA1c ≥9%), or intentional weight loss ≥5% within the prior six months.

Factors:

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

mb_sample_id local_sample_id Sample source Group
SA481266QC(I)#3Instrument QC n/a
SA481267QC(I)#9Instrument QC n/a
SA481268QC(I)#8Instrument QC n/a
SA481269QC(I)#7Instrument QC n/a
SA481270QC(I)#6Instrument QC n/a
SA481271QC(I)#5Instrument QC n/a
SA481272QC(I)#4Instrument QC n/a
SA481273QC(I)#1Instrument QC n/a
SA481274QC(I)#2Instrument QC n/a
SA48127568Muscle WeightLoss
SA48127637Muscle WeightLoss
SA4812777Muscle WeightLoss
SA48127847Muscle WeightLoss
SA4812796Muscle WeightLoss
SA48128051Muscle WeightLoss
SA48128152Muscle WeightLoss
SA48128258Muscle WeightLoss
SA48128360Muscle WeightLoss
SA48128469Muscle WeightLoss
SA48128535Muscle WeightLoss
SA48128670Muscle WeightLoss
SA4812873Muscle WeightLoss
SA48128871Muscle WeightLoss
SA48128972Muscle WeightLoss
SA48129073Muscle WeightLoss
SA48129176Muscle WeightLoss
SA48129279Muscle WeightLoss
SA4812931Muscle WeightLoss
SA48129436Muscle WeightLoss
SA48129550Muscle WeightLoss
SA48129633Muscle WeightLoss
SA48129729Muscle WeightLoss
SA48129831Muscle WeightLoss
SA48129912Muscle WeightLoss
SA48130013Muscle WeightLoss
SA48130121Muscle WeightLoss
SA48130263Muscle WeightStable
SA48130365Muscle WeightStable
SA48130466Muscle WeightStable
SA48130567Muscle WeightStable
SA48130623Muscle WeightStable
SA48130722Muscle WeightStable
SA48130817Muscle WeightStable
SA48130910Muscle WeightStable
SA48131018Muscle WeightStable
SA48131132Muscle WeightStable
SA48131274Muscle WeightStable
SA48131375Muscle WeightStable
SA48131416Muscle WeightStable
SA48131577Muscle WeightStable
SA48131680Muscle WeightStable
SA48131781Muscle WeightStable
SA48131862Muscle WeightStable
SA4813195Muscle WeightStable
SA48132024Muscle WeightStable
SA48132149Muscle WeightStable
SA48132238Muscle WeightStable
SA48132340Muscle WeightStable
SA48132441Muscle WeightStable
SA48132543Muscle WeightStable
SA4813269Muscle WeightStable
SA48132748Muscle WeightStable
SA48132845Muscle WeightStable
SA48132927Muscle WeightStable
SA48133026Muscle WeightStable
SA48133154Muscle WeightStable
SA48133256Muscle WeightStable
SA48133357Muscle WeightStable
SA48133425Muscle WeightStable
SA48133559Muscle WeightStable
SA481336QC(S)#6Sample QC (pooled study samples) n/a
SA481337QC(S)#3Sample QC (pooled study samples) n/a
SA481338QC(S)#8Sample QC (pooled study samples) n/a
SA481339QC(S)#7Sample QC (pooled study samples) n/a
SA481340QC(S)#1Sample QC (pooled study samples) n/a
SA481341QC(S)#5Sample QC (pooled study samples) n/a
SA481342QC(S)#4Sample QC (pooled study samples) n/a
SA481343QC(S)#9Sample QC (pooled study samples) n/a
SA481344QC(S)#2Sample QC (pooled study samples) n/a
Showing results 1 to 79 of 79

Collection:

Collection ID:CO004310
Collection Summary:Rectus abdominis biopsies (0.5–1.0 g) were collected via transverse incision and sharp dissection during laparotomies. Specimens were quickly and grossly dissected to remove cauterized edges or vascular tissue, then immediately flash frozen using liquid nitrogen and stored at −80°C until analysis.
Sample Type:Muscle

Treatment:

Treatment ID:TR004326
Treatment Summary:n/a

Sample Preparation:

Sampleprep ID:SP004323
Sampleprep Summary:Approximately 1.0 mg rectus abdominis was sent to the Northwest Metabolomics Research Center at the University of Washington for performance of targeted metabolomics. In brief, targeted liquid chromatography mass spectrometry using a HILIC column to separate polar, aqueous metabolite analysis was performed. The assay targets over 350 metabolites from more than 60 metabolic pathways using a Sciex 6500+ platform and Aciex Analyst software for peak integration. All mass spectrometry experiments also included blank samples run under identical conditions to identify any signals arising from solvents/reagents/buffers that may also affect batch-to-batch variation. Muscle metabolite abundance was normalized to protein loading and expressed as relative concentration.

Chromatography:

Chromatography ID:CH005252
Chromatography Summary:10 µL for analysis using negative (NEG) ionization mode
Instrument Name:Shimadzu Nexera XR LC-20AD
Column Name:Waters XBridge BEH Amide (150 x 2.1 mm, 2.5 µm)
Column Temperature:45°C
Flow Gradient:[0-1.5 min: 5% A , 95% B; 1.5-6 min: 5-30% A, 95-70% B; 6-10 min: 30% A - 70% B; 10-12 min: 30-55% A, 70-45 % B; 12-14 min: 55% A , 45% B; 14-15 min: 55-5% A, 45-95% B; 15-18 min: 5% A, 95%]
Flow Rate:0.3 mL/min
Solvent A:95% Water/3% acetonitrile/2% methanol; 10 mM ammonium acetate; 0.2% acetic acid
Solvent B:93% Acetonitrile/5% water/2% methanol; 10 mM ammonium acetate; 0.2% acetic acid
Chromatography Type:HILIC
  
Chromatography ID:CH005253
Chromatography Summary:5 µL for analysis using positive (POS) ionization mode
Instrument Name:Shimadzu Nexera XR LC-20AD
Column Name:Waters XBridge BEH Amide (150 x 2.1 mm, 2.5 µm)
Column Temperature:45°C
Flow Gradient:[0-13 min: 5% A , 95% B; 3-8 min: 5-30% A, 95-50% B; 18-12 min: 50% A, 50% B; 12-13 min: 50-5% A, 50-95% B; 13-15 min: 5% A, 95% B]
Flow Rate:0.3 mL/min
Solvent A:95% Water/5% methanol; 10 mM ammonium acetate; 0.3% acetic acid
Solvent B:90% Acetonitrile/5% Water/5% methanol; 10 mM ammonium acetate; 0.3% acetic acid
Chromatography Type:HILIC

Analysis:

Analysis ID:AN006915
Analysis Type:MS
Chromatography ID:CH005252
Num Factors:4
Num Metabolites:203
Units:ion counts/second
  
Analysis ID:AN006916
Analysis Type:MS
Chromatography ID:CH005253
Num Factors:4
Num Metabolites:154
Units:ion counts/second
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