Liquid biopsy with droplet digital PCR targeted to specific mutations in plasma cell-free tumor DNA can detect ovarian cancer recurrence earlier than CA125

Takamichi Minato, Shin Ito, Bin Li, Haruna Fujimori, Mai Mochizuki, Kazunori Yamaguchi, Keiichi Tamai, Muneaki Shimada, Hideki Tokunaga, Shogo Shigeta, Ikuro Sato, Hiroshi Shima, Hidekazu Yamada, Nobuo Yaegashi, Jun Yasuda

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Ovarian cancer (OC) is an intractable gynecological tumor, and frequent recurrence is experienced within a few years even after the complete eradication of tumor tissues by radical resection and neo-adjuvant chemotherapies. The conventional recurrence marker, CA125, is widely used for follow-up after resection of OC, but CA125 has a long half-life in blood and lacks dynamic responses to tumor recurrence. Recent developments in liquid biopsy procedures are expected to overcome the difficulties in early diagnosis of OC recurrence after surgery. Methods: We applied droplet digital PCR (ddPCR) technology to detect circulating tumor-derived DNA in OC patients’ plasma during follow-up. Exome sequencing of 11 tumor–normal pairs of genomic DNA from consecutive OC patients identified tumor-specific mutations, and ddPCR probes were selected for each sample. Results: Six of 11 cases showed apparent recurrence during follow-up (mean progression-free survival was 348.3 days) and all six cases were positive in ddPCR analyses. In addition, ddPCR became positive before increased plasma CA125 in five out of six cases. Increased allele frequency of circulating tumor DNA (ctDNA) is associated with increased tumor volume after recurrence. ddPCR detected ctDNA signals significantly earlier than increased CA125 in the detection of OC recurrence by imaging (49 days and 7 days before, respectively: p < 0.05). No ctDNA was detected in the plasma of recurrence-free cases. Conclusions: Our results demonstrate the potential of identifying ctDNA by ddPCR as an early detection tool for OC recurrence.

Original languageEnglish
Article number100847
JournalGynecologic Oncology Reports
Volume38
DOIs
Publication statusPublished - 2021 Nov

Keywords

  • CA125
  • ctDNA
  • ddPCR
  • Ovarian cancer

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

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