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 Nishimura, Ayano Takeuchi, Yutaka Endo, Osamu Itano, Yuukou Kitagawa

Research output: Contribution to journalArticle

9 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

Fingerprint

Pancreatic Neoplasms
Retrospective Studies
Mutation
DNA
Serum
Adenocarcinoma
Biomarkers
Peptide Nucleic Acids
Pancreatectomy
Survival
Constriction
Codon
Disease-Free Survival
Multivariate Analysis
Confidence Intervals
Polymerase Chain Reaction
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

KRAS mutations in cell-free DNA from preoperative and postoperative sera as a pancreatic cancer marker : A retrospective study. / Nakano, Yutaka; Kitago, Minoru; Matsuda, Sachiko; Nakamura, Yuki; Fujita, Yusuke; Imai, Shunichi; Shinoda, Masahiro; Yagi, Hiroshi; Abe, Yuta; Hibi, Taizo; Nishimura, Yoko; Takeuchi, Ayano; Endo, Yutaka; Itano, Osamu; Kitagawa, Yuukou.

In: British Journal of Cancer, Vol. 118, No. 5, 06.03.2018, p. 662-669.

Research output: Contribution to journalArticle

Nakano, Yutaka ; Kitago, Minoru ; Matsuda, Sachiko ; Nakamura, Yuki ; Fujita, Yusuke ; Imai, Shunichi ; Shinoda, Masahiro ; Yagi, Hiroshi ; Abe, Yuta ; Hibi, Taizo ; Nishimura, Yoko ; Takeuchi, Ayano ; Endo, Yutaka ; Itano, Osamu ; Kitagawa, Yuukou. / KRAS mutations in cell-free DNA from preoperative and postoperative sera as a pancreatic cancer marker : A retrospective study. In: British Journal of Cancer. 2018 ; Vol. 118, No. 5. pp. 662-669.
@article{cc2e18435f09470590eb36e3abd8e16f,
title = "KRAS mutations in cell-free DNA from preoperative and postoperative sera as a pancreatic cancer marker: A retrospective study",
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.",
author = "Yutaka Nakano and Minoru Kitago and Sachiko Matsuda and Yuki Nakamura and Yusuke Fujita and Shunichi Imai and Masahiro Shinoda and Hiroshi Yagi and Yuta Abe and Taizo Hibi and Yoko Nishimura and Ayano Takeuchi and Yutaka Endo and Osamu Itano and Yuukou Kitagawa",
year = "2018",
month = "3",
day = "6",
doi = "10.1038/bjc.2017.479",
language = "English",
volume = "118",
pages = "662--669",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - KRAS mutations in cell-free DNA from preoperative and postoperative sera as a pancreatic cancer marker

T2 - A retrospective study

AU - Nakano, Yutaka

AU - Kitago, Minoru

AU - Matsuda, Sachiko

AU - Nakamura, Yuki

AU - Fujita, Yusuke

AU - Imai, Shunichi

AU - Shinoda, Masahiro

AU - Yagi, Hiroshi

AU - Abe, Yuta

AU - Hibi, Taizo

AU - Nishimura, Yoko

AU - Takeuchi, Ayano

AU - Endo, Yutaka

AU - Itano, Osamu

AU - Kitagawa, Yuukou

PY - 2018/3/6

Y1 - 2018/3/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85043279153&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85043279153&partnerID=8YFLogxK

U2 - 10.1038/bjc.2017.479

DO - 10.1038/bjc.2017.479

M3 - Article

VL - 118

SP - 662

EP - 669

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 5

ER -