Fragmentomics features of ovarian cancer

Int J Cancer. 2024 Oct 1;155(7):1316-1326. doi: 10.1002/ijc.34981. Epub 2024 May 20.

Abstract

Ovarian cancer (OC) is a major cause of cancer mortality in women worldwide. Due to the occult onset of OC, its nonspecific clinical symptoms in the early phase, and a lack of effective early diagnostic tools, most OC patients are diagnosed at an advanced stage. In this study, shallow whole-genome sequencing was utilized to characterize fragmentomics features of circulating tumor DNA (ctDNA) in OC patients. By applying a machine learning model, multiclass fragmentomics data achieved a mean area under the curve (AUC) of 0.97 (95% CI 0.962-0.976) for diagnosing OC. OC scores derived from this model strongly correlated with the disease stage. Further comparative analysis of OC scores illustrated that the fragmentomics-based technology provided additional clinical benefits over the traditional serum biomarkers cancer antigen 125 (CA125) and the Risk of Ovarian Malignancy Algorithm (ROMA) index. In conclusion, fragmentomics features in ctDNA are potential biomarkers for the accurate diagnosis of OC.

Keywords: differentiating; fragmentomics; machine learning; ovarian cancer; screening.

MeSH terms

  • Adult
  • Aged
  • Algorithms
  • Area Under Curve
  • Biomarkers, Tumor* / blood
  • Biomarkers, Tumor* / genetics
  • CA-125 Antigen / blood
  • Circulating Tumor DNA* / blood
  • Circulating Tumor DNA* / genetics
  • Female
  • Humans
  • Machine Learning*
  • Middle Aged
  • Ovarian Neoplasms* / blood
  • Ovarian Neoplasms* / diagnosis
  • Ovarian Neoplasms* / genetics
  • Whole Genome Sequencing / methods

Substances

  • Biomarkers, Tumor
  • Circulating Tumor DNA
  • CA-125 Antigen