Summary of Study ST001013

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 PR000680. The data can be accessed directly via it's Project DOI: 10.21228/M8S684 This work is supported by NIH grant, U2C- DK119886.

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Study IDST001013
Study TitleTCA Concentrations in Serum for Muscle Wasting in Cancer Cachexia (part-VIII)
Study SummaryTCA Concentrations of Muscle Wasting in Cancer Cachexia. Serum samples from 10 control patients, 10 weight stable pancreatic cancer patients, and 10 pancreatic cancer patients with significant weight loss. Samples are divided evenly between males and females.
Institute
Mayo Clinic
Last NameGuttridge
First NameDenis
Address520 Biomedical Research Tower 460 W. 12th Avenue Columbus, OH 43210
Emaildenis.guttridge@osumc.edu
Phone614-688-3137
Submit Date2018-07-15
Analysis Type DetailGC-MS
Release Date2020-07-15
Release Version1
Denis Guttridge Denis Guttridge
https://dx.doi.org/10.21228/M8S684
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000680
Project DOI:doi: 10.21228/M8S684
Project Title:Mayo Pilot and Feasibility: Metabolomics of Muscle Wasting in Cancer Cachexia
Project Summary:Cachexia is a debilitating syndrome that results in severe, involuntary weight loss due to the depletion of skeletal muscle mass. This syndrome occurs in a majority of cancers and contributes to approximately one third of all cancer deaths. Currently, no effective therapy exists to combat this malignant disorder, and disappointing results from recent Phase III clinical trials indicate that a cachexia treatment is not likely to appear soon. Thus, it is clear that greater knowledge of the mechanisms driving muscle wasting in cachexia is needed in order to identify new therapeutic targets and stimulate new clinical trials. Our approach to gaining this knowledge has been to work with muscle biopsies from pancreatic cancer patients, since this population is highly prone to cachexia. We have also been expanding our studies beyond the classical mouse models of cancer cachexia in hopes of finding a new model that better recapitulates the human disease. We recently undertook RNA-Seq analysis comparing muscle biopsies from pancreatic cancer patients with and without cachexia, which has been exciting since this type of analysis has not yet been performed in patient samples. Preliminary results revealed that cachectic muscle was associated with alterations in metabolism. These data provide the rationale for performing metabolomics to ascertain whether specific metabolic pathways or metabolites can be identified as potential drivers of muscle wasting in cachexia or be used as biomarker of cachexia, which the field desperately needs. An additional need is a well-validated animal model of cancer cachexia that accurately reflects the human condition, which can be used to test mechanisms and pre-clinical compounds. We propose to perform these studies under the Mayo Clinic Metabolomics Resource Core Pilot and Feasibility Grant program to: 1) Identify metabolic alterations and biomarkers of pancreatic cancer-induced muscle wasting; and 2) Identify a suitable mouse model that recapitulates the metabolic imbalance of muscles from pancreatic cancer cachexia patients. By performing these studies, we will accelerate our understanding of the underlying causes of muscle wasting, which should translate to improving the current pipeline of anticachexia therapies.
Institute:Mayo Clinic
Last Name:Guttridge
First Name:Denis
Address:520 Biomedical Research Tower 460 W. 12th Avenue Columbus, OH 43210
Email:denis.guttridge@osumc.edu
Phone:614-688-3137

Subject:

Subject ID:SU001052
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 Grouping Gender
SA063582Sample # 18Control Female
SA063583Sample # 7Control Female
SA063584Sample # 9Control Female
SA063585Sample # 4Control Female
SA063586Sample # 3Control Female
SA063587Sample # 10Control Male
SA063588Sample # 20Control Male
SA063589Sample # 27Control Male
SA063590Sample # 15Control Male
SA063591Sample # 2Control Male
SA063592Sample # 1Weight Losing Female
SA063593Sample # 22Weight Losing Female
SA063594Sample # 21Weight Losing Female
SA063595Sample # 26Weight Losing Female
SA063596Sample # 29Weight Losing Female
SA063597Sample # 6Weight Losing Male
SA063598Sample # 5Weight Losing Male
SA063599Sample # 14Weight Losing Male
SA063600Sample # 30Weight Losing Male
SA063601Sample # 13Weight Losing Male
SA063602Sample # 25Weight Stable Female
SA063603Sample # 24Weight Stable Female
SA063604Sample # 16Weight Stable Female
SA063605Sample # 17Weight Stable Female
SA063606Sample # 19Weight Stable Female
SA063607Sample # 8Weight Stable Male
SA063608Sample # 11Weight Stable Male
SA063609Sample # 28Weight Stable Male
SA063610Sample # 23Weight Stable Male
SA063611Sample # 12Weight Stable Male
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Collection:

Collection ID:CO001046
Collection Summary:Tissue and blood donated from Cancer Cachexia Program at Ohio State University
Sample Type:Blood (serum)

Treatment:

Treatment ID:TR001066
Treatment Summary:Cancer cachexia is a multi-factorial syndrome accompanying advanced cancer, with the most notable symptom being unintentional weight loss. Cachectic patients lose both adipose tissue and skeletal muscle, with skeletal muscle loss and its associated weakness contributing to the morbidity and mortality of these patients. Despite three decades of research into mechanisms driving muscle wasting due to cancer, to date, an approved pharmacological therapy to prevent or treat cancer cachexia is still lacking. Our laboratory focuses on cancer cachexia in patients with pancreatic cancer, as up to 85% of these patients experience weight loss. Cachexia often occurs early in the progression of pancreatic cancer, making clear that cachexia in these patients is not simply a result of end-stage disease. Further, with perhaps more than ¼ of all pancreatic cancer deaths resulting from muscle weakness as opposed to tumor burden, cachexia also significantly contributes to mortality due to pancreatic cancer. Because little progress has been made in improving treatment outcomes, addressing cancer-induced muscle wasting is perhaps the best strategy to prolong pancreatic cancer patient survival and increase patient quality of life. In an effort to better understand the mechanisms driving pancreatic cancer-induced muscle wasting, the Cancer Cachexia Program at Ohio State University has begun a Pancreatic Cancer Cachexia Tissue Bank. To date, over 130 patients undergoing attempted resection for pancreatic cancer or other abdominal surgeries have donated muscle and blood to our bank. A unique aspect of our tissue bank is our focus on patients eligible for resection. In contrast to other studies using patients with late-stage disease, our patients are not end-stage, as they are considered healthy enough to undergo a major operation.

Sample Preparation:

Sampleprep ID:SP001059
Sampleprep Summary:TCA concentrations using serum

Combined analysis:

Analysis ID AN001655
Analysis type MS
Chromatography type GC
Chromatography system Agilent 7890B
Column Agilent HP5-MS (30m × 0.25mm, 0.25 um)
MS Type EI
MS instrument type Single quadrupole
MS instrument name Agilent 5977A
Ion Mode POSITIVE
Units uM

Chromatography:

Chromatography ID:CH001166
Instrument Name:Agilent 7890B
Column Name:Agilent HP5-MS (30m × 0.25mm, 0.25 um)
Chromatography Type:GC

MS:

MS ID:MS001530
Analysis ID:AN001655
Instrument Name:Agilent 5977A
Instrument Type:Single quadrupole
MS Type:EI
Ion Mode:POSITIVE
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