Early changes of muscle insulin-like growth factor-1 and myostatin gene expression in gastric cancer patients

Muscle Nerve. 2013 Sep;48(3):387-92. doi: 10.1002/mus.23798. Epub 2013 Jul 17.

Abstract

Introduction: Cachexia increases morbidity and mortality of cancer patients. The progressive loss of muscle mass negatively affects physical function and quality of life. We previously showed reduced muscle insulin-like growth factor-1 (IGF-1) expression and enhanced myostatin signaling in tumor-bearing animals. This study was aimed at investigating whether similar perturbations occur in gastric cancer patients.

Methods: Early perturbations of myostatin and IGF-1 signaling (including the expression of muscle-specific ubiquitin ligases) were investigated in 16 gastric cancer patients and in 6 controls by analyzing muscle mRNA expression with semiquantitative reverse transcriptase polymerase chain reaction (PCR) and real-time PCR.

Results: In gastric cancer patients, muscle mRNA levels for IGF-1, myostatin, and atrogin-1 were reduced irrespective of weight loss (≤5% or >5%), whereas MuRF1 expression was unchanged.

Conclusions: IGF-1 and myostatin mRNA levels are downregulated in gastric cancer patients who have minimal or no weight loss. These early alterations are particularly relevant in order to devise preventive and therapeutic strategies for cancer cachexia.

Keywords: IGF-1; cachexia; human cancer; myostatin; ubiquitin ligases.

MeSH terms

  • Aged
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Middle Aged
  • Muscle Proteins / genetics
  • Muscles / metabolism*
  • Myostatin / genetics
  • Myostatin / metabolism*
  • RNA, Messenger / metabolism
  • SKP Cullin F-Box Protein Ligases / genetics
  • Statistics, Nonparametric
  • Stomach Neoplasms / pathology*
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / genetics

Substances

  • MSTN protein, human
  • Muscle Proteins
  • Myostatin
  • RNA, Messenger
  • Tripartite Motif Proteins
  • Insulin-Like Growth Factor I
  • FBXO32 protein, human
  • SKP Cullin F-Box Protein Ligases
  • TRIM63 protein, human
  • Ubiquitin-Protein Ligases