KRAS mutations in cell-free DNA from preoperative and postoperative sera as a pancreatic cancer marker: A retrospective study

Yutaka Nakano, Minoru Kitago, Sachiko Matsuda, Yuki Nakamura, Yusuke Fujita, Shunichi Imai, Masahiro Shinoda, Hiroshi Yagi, Yuta Abe, Taizo Hibi, Yoko Fujii-Nishimura, Ayano Takeuchi, Yutaka Endo, Osamu Itano, Yuko Kitagawa

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background:Pancreatic ductal adenocarcinoma (PDAC) has very poor prognosis despite existing multimodal therapies. This study aimed to investigate whether KRAS mutations at codons 12/13 in cell-free DNA (cfDNA) from preoperative and postoperative sera from patients with PDAC can serve as a predictive biomarker for treatment response and outcomes after surgery.Methods:Preoperative and postoperative serum samples obtained from 45 patients with PDAC whom underwent curative pancreatectomy at our institution between January 2013 and July 2016 were retrospectively analysed. Peptide nucleic acid-directed PCR clamping was used to identify KRAS mutations in cfDNA.Results:Among the 45 patients enrolled, 11 (24.4%) and 20 (44.4%) had KRAS mutations in cfDNA from preoperative and postoperative sera, respectively. Multivariate analysis revealed that KRAS mutations in postoperative serum (hazard ratio (HR)=2.919; 95% confidence interval (CI)=1.109-5.621; P=0.027) are an independent prognostic factor for disease-free survival. Furthermore, the shift from wild-type KRAS in preoperative to mutant KRAS in postoperative cfDNA (HR=9.419; 95% Cl=2.015-44.036; P=0.004) was an independent prognostic factor for overall survival.Conclusions:Changes in KRAS mutation status between preoperative and postoperative cfDNA may be a useful predictive biomarker for survival and treatment response.

Original languageEnglish
Pages (from-to)662-669
Number of pages8
JournalBritish Journal of Cancer
Volume118
Issue number5
DOIs
Publication statusPublished - 2018 Mar 6

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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