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This study reveals that age and gender impact nuclear circulating DNA (NcirDNA) in healthy individuals, but not in metastatic colorectal cancer (mCRC) patients. Mitochondrial circulating DNA (McirDNA) levels differ significantly between healthy individuals and mCRC patients.

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Area of Science:

  • Biochemistry
  • Genetics
  • Oncology

Background:

  • Circulating DNA (cirDNA) in plasma, including nuclear (NcirDNA) and mitochondrial (McirDNA) components, is a promising biomarker.
  • Variability in cirDNA quantification can arise from pre-analytical and demographic factors, potentially affecting its clinical utility.

Purpose of the Study:

  • To comprehensively investigate the influence of pre-analytical and demographic parameters on NcirDNA and McirDNA quantification.
  • To compare cirDNA levels between healthy individuals and patients with metastatic colorectal cancer (mCRC).

Main Methods:

  • Analysis of plasma samples from 222 subjects (104 healthy, 118 mCRC patients).
  • Quantification of NcirDNA and McirDNA using established molecular techniques.
  • Statistical analysis, including univariate and multivariate analyses, to assess the impact of age, gender, and pre-analytical factors.

Main Results:

  • NcirDNA concentration was significantly influenced by age and gender in healthy individuals, with age over 47 being predictive of higher levels.
  • McirDNA concentration was independent of age and gender in healthy individuals.
  • In mCRC patients, both NcirDNA and McirDNA levels were independent of the investigated demographic and pre-analytical factors.
  • Significant differences in NcirDNA, McirDNA, and the McirDNA/NcirDNA ratio were observed between mCRC patients and healthy individuals (p < 0.0001).

Conclusions:

  • Demographic factors like age and gender play a role in NcirDNA levels in healthy individuals, but not in mCRC patients.
  • McirDNA levels are significantly elevated in mCRC patients compared to healthy controls.
  • NcirDNA and McirDNA do not exhibit similar variation patterns concerning health status and demographic/pre-analytical factors, suggesting distinct biological origins or regulation.