Evaluation of circulating tumor DNA as a biomarker in pancreatic cancer with liver metastasis

PLoS One. 2020 Jul 2;15(7):e0235623. doi: 10.1371/journal.pone.0235623. eCollection 2020.

Abstract

Pancreatic cancer is an aggressive, solid tumor, with a grave prognosis. Despite surgical treatment in patients with pancreatic cancer, the rate of recurrence is high. In addition, although tumor biomarkers are frequently used to confirm advanced pancreatic cancer, this is not accurate and the biomarkers currently used cannot indicate prognosis. This study sought to evaluate circulating tumor DNA as a tumor biomarker to prognosticate pancreatic cancer. Patients with advanced pancreatic cancer and liver metastasis (N = 104) were included, and blood samples were collected from all patients. The mutant allele frequency was measured using amplicon-based deep sequencing on a cell-free DNA panel covering 14 genes with > 240 hot spots. In patients with advanced pancreatic cancer, 50% (N = 52) had detectable ctDNA levels, with TP53 (45%, N = 47) and KRAS (42.3%, N = 44) mutations the most common. Patients with detectable circulating tumor DNA levels also had significantly worse overall survival and progression free survival than ctDNA negative patients (8.4 vs 16 months, P<0.0001 for overall survival; 3.2 vs 7.9 months, P<0.0001 for progression-free survival). In a multivariate analysis, ctDNA status was independently associated with overall survival and progression-free survival (HR = 3.1, 95%CI = 1.9-5.0, P<0.0001; HR 2.6, 95%CI = 1.7-4.0, P<0.0001, respectively). Moreover, circulating tumor DNA significantly correlated with a higher number of liver metastases, the presence of lung and/or peritoneal metastases, tumor burden, and higher carbohydrate antigen 19-9 levels. This study supports the use of circulating tumor DNA as an independent prognostic marker for advanced pancreatic cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • CA-19-9 Antigen / blood
  • Cell-Free Nucleic Acids / metabolism
  • Circulating Tumor DNA / blood*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Prognosis
  • Progression-Free Survival
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • CA-19-9 Antigen
  • Cell-Free Nucleic Acids
  • Circulating Tumor DNA
  • KRAS protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins p21(ras)

Grants and funding

The author(s) received no specific funding for this work.