Plasma metabolomics identifies lipid and amino acid markers of weight loss in patients with upper gastrointestinal cancer

Janice Miller, Ahmed Alshehri, Michael I. Ramage, Nathan A. Stevens, Alexander B. Mullen, Marie Boyd, James A. Ross, Stephen J. Wigmore, David G. Watson, Richard J.E. Skipworth

Research output: Contribution to journalArticle

Abstract

Cachexia is a multifactorial wasting syndrome associated with high morbidity and mortality in patients with cancer. Diagnosis can be difficult and, in the clinical situation, usually relies upon reported weight loss. The 'omics' technologies allow us the opportunity to study the end points of many biological processes. Among these, blood-based metabolomics is a promising method to investigate the pathophysiology of human cancer cachexia and identify candidate biomarkers. In this study, we performed liquid chromatography mass spectrometry (LC/MS)-based metabolomics to investigate the metabolic profile of cancer-associated weight loss. Non-selected patients undergoing surgery with curative intent for upper gastrointestinal cancer were recruited. Fasting plasma samples were taken at induction of anaesthesia. LC/MS analysis showed that 6 metabolites were highly discriminative of weight loss. Specifically, a combination profile of LysoPC 18.2, L-Proline, Hexadecanoic acid, Octadecanoic acid, Phenylalanine and LysoPC 16:1 showed close correlation for eight weight-losing samples (≥5% weight loss) and nine weight-stable samples (<5%weight loss) between predicted and actual weight change (r = 0.976, p = 0.0014). Overall, 40 metabolites were associated with ≥5% weight loss. This study provides biological validation of the consensus definition of cancer cachexia (Fearon et al.) and provides feasible candidate markers for further investigation in early diagnosis and the assessment of therapeutic intervention.

LanguageEnglish
Article number1594
Number of pages11
JournalCancers
Volume11
Issue number10
DOIs
Publication statusPublished - 19 Oct 2019

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Gastrointestinal Neoplasms
Metabolomics
Weight Loss
Lipids
Amino Acids
Cachexia
Weights and Measures
Liquid Chromatography
Mass Spectrometry
Neoplasms
Wasting Syndrome
Biological Phenomena
Metabolome
Palmitic Acid
Phenylalanine
Proline
Early Diagnosis
Fasting
Anesthesia
Biomarkers

Keywords

  • cancer
  • metabolomics
  • cachexia
  • high resolution mass spectrometry

Cite this

Miller, Janice ; Alshehri, Ahmed ; Ramage, Michael I. ; Stevens, Nathan A. ; Mullen, Alexander B. ; Boyd, Marie ; Ross, James A. ; Wigmore, Stephen J. ; Watson, David G. ; Skipworth, Richard J.E. / Plasma metabolomics identifies lipid and amino acid markers of weight loss in patients with upper gastrointestinal cancer. 2019 ; Vol. 11, No. 10.
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abstract = "Cachexia is a multifactorial wasting syndrome associated with high morbidity and mortality in patients with cancer. Diagnosis can be difficult and, in the clinical situation, usually relies upon reported weight loss. The 'omics' technologies allow us the opportunity to study the end points of many biological processes. Among these, blood-based metabolomics is a promising method to investigate the pathophysiology of human cancer cachexia and identify candidate biomarkers. In this study, we performed liquid chromatography mass spectrometry (LC/MS)-based metabolomics to investigate the metabolic profile of cancer-associated weight loss. Non-selected patients undergoing surgery with curative intent for upper gastrointestinal cancer were recruited. Fasting plasma samples were taken at induction of anaesthesia. LC/MS analysis showed that 6 metabolites were highly discriminative of weight loss. Specifically, a combination profile of LysoPC 18.2, L-Proline, Hexadecanoic acid, Octadecanoic acid, Phenylalanine and LysoPC 16:1 showed close correlation for eight weight-losing samples (≥5{\%} weight loss) and nine weight-stable samples (<5{\%}weight loss) between predicted and actual weight change (r = 0.976, p = 0.0014). Overall, 40 metabolites were associated with ≥5{\%} weight loss. This study provides biological validation of the consensus definition of cancer cachexia (Fearon et al.) and provides feasible candidate markers for further investigation in early diagnosis and the assessment of therapeutic intervention.",
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Plasma metabolomics identifies lipid and amino acid markers of weight loss in patients with upper gastrointestinal cancer. / Miller, Janice; Alshehri, Ahmed; Ramage, Michael I.; Stevens, Nathan A.; Mullen, Alexander B.; Boyd, Marie; Ross, James A.; Wigmore, Stephen J.; Watson, David G.; Skipworth, Richard J.E.

Vol. 11, No. 10, 1594, 19.10.2019.

Research output: Contribution to journalArticle

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AU - Miller, Janice

AU - Alshehri, Ahmed

AU - Ramage, Michael I.

AU - Stevens, Nathan A.

AU - Mullen, Alexander B.

AU - Boyd, Marie

AU - Ross, James A.

AU - Wigmore, Stephen J.

AU - Watson, David G.

AU - Skipworth, Richard J.E.

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