Summary of Study ST004161

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 PR002622. The data can be accessed directly via it's Project DOI: 10.21228/M8QR9D 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.

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Study IDST004161
Study TitleDistinct plasma 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 Date2025-08-28
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/M8QR9D
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR002622
Project DOI:doi: 10.21228/M8QR9D
Project Title:Distinct plasma 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:SU004312
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
SA480881QC(I)#2Instrument QC n/a
SA480882QC(I)#10Instrument QC n/a
SA480883QC(I)#9Instrument QC n/a
SA480884QC(I)#8Instrument QC n/a
SA480885QC(I)#7Instrument QC n/a
SA480886QC(I)#6Instrument QC n/a
SA480887QC(I)#5Instrument QC n/a
SA480888QC(I)#4Instrument QC n/a
SA480889QC(I)#3Instrument QC n/a
SA480890QC(I)#1Instrument QC n/a
SA48089142Plasma WeightLoss
SA4808923Plasma WeightLoss
SA48089373Plasma WeightLoss
SA48089472Plasma WeightLoss
SA48089571Plasma WeightLoss
SA48089635Plasma WeightLoss
SA48089736Plasma WeightLoss
SA48089837Plasma WeightLoss
SA48089970Plasma WeightLoss
SA48090029Plasma WeightLoss
SA48090169Plasma WeightLoss
SA4809026Plasma WeightLoss
SA48090368Plasma WeightLoss
SA48090450Plasma WeightLoss
SA48090560Plasma WeightLoss
SA48090658Plasma WeightLoss
SA4809077Plasma WeightLoss
SA48090831Plasma WeightLoss
SA48090989Plasma WeightLoss
SA48091011Plasma WeightLoss
SA48091113Plasma WeightLoss
SA48091282Plasma WeightLoss
SA4809131Plasma WeightLoss
SA48091421Plasma WeightLoss
SA48091587Plasma WeightLoss
SA4809168Plasma WeightLoss
SA48091720Plasma WeightLoss
SA48091879Plasma WeightLoss
SA48091965Plasma WeightStable
SA4809204Plasma WeightStable
SA48092161Plasma WeightStable
SA48092262Plasma WeightStable
SA48092363Plasma WeightStable
SA48092474Plasma WeightStable
SA48092566Plasma WeightStable
SA48092667Plasma WeightStable
SA48092790Plasma WeightStable
SA48092888Plasma WeightStable
SA48092983Plasma WeightStable
SA4809302Plasma WeightStable
SA48093156Plasma WeightStable
SA48093280Plasma WeightStable
SA48093357Plasma WeightStable
SA48093410Plasma WeightStable
SA48093555Plasma WeightStable
SA48093638Plasma WeightStable
SA48093715Plasma WeightStable
SA48093816Plasma WeightStable
SA48093917Plasma WeightStable
SA48094018Plasma WeightStable
SA48094122Plasma WeightStable
SA48094223Plasma WeightStable
SA48094324Plasma WeightStable
SA48094425Plasma WeightStable
SA48094526Plasma WeightStable
SA48094627Plasma WeightStable
SA48094732Plasma WeightStable
SA48094854Plasma WeightStable
SA48094934Plasma WeightStable
SA48095039Plasma WeightStable
SA48095143Plasma WeightStable
SA48095253Plasma WeightStable
SA48095349Plasma WeightStable
SA48095448Plasma WeightStable
SA48095546Plasma WeightStable
SA4809565Plasma WeightStable
SA48095741Plasma WeightStable
SA48095840Plasma WeightStable
SA480959QC(S)#1Sample QC (pooled study samples) n/a
SA480960QC(S)#8Sample QC (pooled study samples) n/a
SA480961QC(S)#4Sample QC (pooled study samples) n/a
SA480962QC(S)#5Sample QC (pooled study samples) n/a
SA480963QC(S)#3Sample QC (pooled study samples) n/a
SA480964QC(S)#7Sample QC (pooled study samples) n/a
SA480965QC(S)#2Sample QC (pooled study samples) n/a
SA480966QC(S)#6Sample QC (pooled study samples) n/a
SA480967QC(S)#10Sample QC (pooled study samples) n/a
SA480968QC(S)#9Sample QC (pooled study samples) n/a
Showing results 1 to 88 of 88

Collection:

Collection ID:CO004305
Collection Summary:A blood sample was obtained in EDTA-containing vacutainers before 10AM to measure plasma metabolites. Vacutainers were inverted 8-10 times, spun at room for temperature for 10 minutes at 3,500 rpm, and the plasma layer was extracted for storage at −80°C until analysis.
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR004321
Treatment Summary:n/a

Sample Preparation:

Sampleprep ID:SP004318
Sampleprep Summary:Approximately 25 µL plasma were sent to the Northwest Metabolomics Research Center at the University of Washington (Seattle, WA, USA) 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.

Chromatography:

Chromatography ID:CH005244
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% B]
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:CH005245
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:AN006905
Analysis Type:MS
Chromatography ID:CH005244
Num Factors:4
Num Metabolites:206
Units:ion count per second
  
Analysis ID:AN006906
Analysis Type:MS
Chromatography ID:CH005245
Num Factors:4
Num Metabolites:153
Units:ions counts per second
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