Sensitive Detection of Gynecological Cancer Recurrence Using Circulating Tumor DNA and Digital PCR: A Comparative Study with Serum Biochemical Markers

Int J Mol Sci. 2024 Nov 8;25(22):11997. doi: 10.3390/ijms252211997.

Abstract

Early detection of recurrences in gynecological cancers is crucial for women's health. Circulating tumor DNA (ctDNA) analysis through liquid biopsy offers a promising approach for monitoring disease progression and identifying relapses. This study investigated the utility of digital Polymerase Chain Reaction (dPCR) for ctDNA detection in three gynecological cancer patients with clinically confirmed relapses during a two-year post-surgical follow-up. Patient-specific tumor mutations were identified through whole-exome sequencing (WES) and confirmed via Sanger sequencing. dPCR probes targeting these mutations were used to quantify the ctDNA levels in plasma samples collected throughout the follow-up period, and the findings were compared with standard serum biochemical markers. In two patients, persistent positive dPCR signals for the selected mutations were detected after tumor removal, with ctDNA levels progressively increasing even after post-surgical chemotherapy. Notably, dPCR identified elevated ctDNA levels before an increase in the cancer antigen 125 (CA125) biochemical marker was observed. In the third patient, no ctDNA signals from the two selected mutations were detected despite clinical evidence of recurrence, suggesting the emergence of new mutations. While this study highlights the promise of dPCR for early recurrence detection in gynecological cancers, it also underscores the critical need for comprehensive mutation panels to overcome the inherent challenges posed by tumor heterogeneity and the emergence of new mutations during disease progression.

Keywords: biochemical markers; ctDNA; dPCR; gynecological cancer.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Biomarkers, Tumor* / blood
  • Biomarkers, Tumor* / genetics
  • Circulating Tumor DNA* / blood
  • Circulating Tumor DNA* / genetics
  • Female
  • Genital Neoplasms, Female* / blood
  • Genital Neoplasms, Female* / diagnosis
  • Genital Neoplasms, Female* / genetics
  • Humans
  • Liquid Biopsy / methods
  • Middle Aged
  • Mutation
  • Neoplasm Recurrence, Local* / blood
  • Neoplasm Recurrence, Local* / genetics
  • Polymerase Chain Reaction* / methods

Substances

  • Circulating Tumor DNA
  • Biomarkers, Tumor