ACVR2B polymorphism, Adiponectin, and GDF-15 levels as biomarkers for cachexia in gastrointestinal cancer

Sci Rep. 2024 Nov 12;14(1):27714. doi: 10.1038/s41598-024-79176-7.

Abstract

Reversing cancer cachexia remains a challenge. Genetic biomarkers for the early detection of the disease have been explored in order to enable the implementation of preventive measures. We therefore genotyped candidate genes based on cachexia phenotype and quantified adiponectin and GDF-15 levels in cachectic patients with gastrointestinal cancer. Patients with a diagnosis of gastrointestinal cancer were divided into a cachectic and a non-cachectic group after the start of chemotherapy. A control group (no cancer) was also included. We genotyped the following single nucleotide polymorphisms (SNPs) by quantitative PCR: FOXO3 (rs1935949), FOXO3 (rs4946935), ACVR2B (rs2268757), and SELP (rs6136). In addition, we quantified adiponectin and GDF-15 levels by ELISA. The rs2268757 SNP in the ACVR2B gene was associated with the weight loss phenotype in cachectic patients with gastrointestinal cancer (non-cachectic, P = 0.004). Plasma adiponectin levels were higher in cachectic patients compared to controls (P = 0.01) and non-cachectic patients (P = 0.004). GDF-15 was also elevated in cachectic patients compared to controls (P < 0.0001) and non-cachectic patients (P = 0.001). Analysis by sex showed elevated adiponectin levels in men (control, P = 0.01) and cachectic women (control, P = 0.04; non-cachectic, P = 0.01), as well as elevated GDF-15 levels in men (control, P = 0.002) and cachectic women (control, P = 0.002; non-cachectic, P = 0.007). However, there was no significant difference in the levels of these cytokines between cachectic men and women. The results suggest the rs2268757 SNP in the ACVR2B gene, adiponectin, and GDF-15 as potential biomarkers of cachexia in gastrointestinal cancer.

Keywords: Adiponectin; Cachexia; Chemotherapy; Gastrointestinal cancer; Polymorphism.

MeSH terms

  • Activin Receptors, Type II* / genetics
  • Adiponectin* / blood
  • Adiponectin* / genetics
  • Aged
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • Cachexia* / blood
  • Cachexia* / diagnosis
  • Cachexia* / etiology
  • Cachexia* / genetics
  • Case-Control Studies
  • Female
  • Gastrointestinal Neoplasms* / blood
  • Gastrointestinal Neoplasms* / complications
  • Gastrointestinal Neoplasms* / genetics
  • Genotype
  • Growth Differentiation Factor 15* / blood
  • Growth Differentiation Factor 15* / genetics
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*

Substances

  • Growth Differentiation Factor 15
  • Adiponectin
  • Activin Receptors, Type II
  • GDF15 protein, human
  • ACVR2B protein, human
  • Biomarkers, Tumor
  • ADIPOQ protein, human