Synergism of Adipocytokine Profile and ADIPOQ/TNF-α Polymorphisms in NAFLD-associated MetS Predict Colorectal Liver Metastases Outgrowth

Cancer Genomics Proteomics. 2019 Nov-Dec;16(6):519-530. doi: 10.21873/cgp.20154.

Abstract

Background/aim: The aim of this study was to evaluate whether the altered profile of adipocytokine and genetic fingerprint in NAFLD-associated metabolic syndrome "cluster" represents synergistic risk factors predicting onset of liver colorectal cancer metastases.

Materials and methods: A total of 165 colorectal cancer patients were enrolled, 56,3% were with metabolic syndrome/NAFLD. Serum samples were assayed for ADIPOQ, leptin and TNF-a levels by ELISA. ADIPOQ rs266729 C/G and TNF-308 A/G genotypes were analyzed in DNA isolated from whole blood.

Results: Reduction in adiponectin levels and increase in leptin and TNF-α was shown in patients with liver metastases. This trend was influenced by BMI, MetS/NAFLD, and insulin resistance. ADIPOQ G rs266729 and TNF- 308 A allele are associated with obesity, MetS/NAFLD and insulin resistance. ADIPOQ CG/GG and GA/AA TNF-alpha genotypes confer susceptibility to liver metastases.

Conclusion: Obesity and hepatic steatosis significantly favor the development of colorectal cancer liver metastases and the individual adipocytokines genetic profile may play an important predictive role.

Keywords: Adiponectin; NAFLD; TNF-α; colorectal cancer; leptin; metabolic syndrome; obesity.

MeSH terms

  • Adiponectin* / genetics
  • Adiponectin* / metabolism
  • Adult
  • Alleles
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Female
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / pathology
  • Liver Neoplasms* / secondary
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Proteins* / genetics
  • Neoplasm Proteins* / metabolism
  • Non-alcoholic Fatty Liver Disease* / genetics
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Non-alcoholic Fatty Liver Disease* / pathology
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity / pathology
  • Polymorphism, Genetic*
  • Tumor Necrosis Factor-alpha* / genetics
  • Tumor Necrosis Factor-alpha* / metabolism

Substances

  • ADIPOQ protein, human
  • Adiponectin
  • Neoplasm Proteins
  • Tumor Necrosis Factor-alpha