Distinct Metabolomic Alterations Are Associated With Physical Function, Weight Loss, and Muscle Mass in Men With...

Area of Science:

• Metabolomics
• Oncology
• Physiology

Background:

• Cancer cachexia is characterized by involuntary weight and muscle mass loss, leading to functional impairment.
• Current treatments are limited due to a lack of clinically meaningful outcome improvements in trials.
• Metabolomics can reveal cellular function effects and identify mechanisms contributing to poor physical function in cancer cachexia.

Purpose of the Study:

• To investigate distinct metabolic signals in plasma and muscle associated with weight loss, low muscle mass, and impaired physical function in cancer cachexia patients.
• To identify potential biomarkers and therapeutic targets for cancer cachexia.

Main Methods:

• Enrolled 72 patients undergoing elective laparotomy for gastrointestinal or genitourinary cancer.
• Collected fasting plasma, handgrip strength (HGS), stair climb power (SCP), and rectus abdominis muscle samples pre-surgery.
• Analyzed metabolomic perturbations associated with weight loss, muscle cross-sectional area (CSA), HGS, and SCP using statistical tests and pathway analysis.

Main Results:

• Weight loss correlated with altered microbial, amino acid, lipid, and caffeine metabolism in plasma.
• Reduced muscle CSA was linked to altered lipid, galactose, glycerophospholipid, histidine metabolism, and bile secretion pathways in skeletal muscle.
• Worse HGS and SCP showed nominal associations with specific metabolic pathways in plasma and muscle, distinct from those linked to weight loss or low CSA.

Conclusions:

• Significant metabolomic alterations in plasma and muscle are associated with cancer-related weight loss and reduced muscle mass.
• Function-specific metabolic changes were observed for handgrip strength and stair climb power, differing from changes related to weight loss or low muscle mass.
• Further research can refine metabolomic profiles for functional outcomes and guide the development of therapies to improve physical function in cancer cachexia.