Utility of serum DNA as a marker for KRAS mutations in pancreatic cancer tissue

Soichiro Ako, Kazuhiro Nouso, Hideaki Kunugasa, Chihiro Dohi, Hiroshi Matushita, Sho Mizukawa, Shinichiro Muro, Yutaka Akimoto, Daisuke Uchida, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hironari Katou, Hiroyuki Okada

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background/Objectives The detection of cancer-specific DNA in peripheral blood, known as a liquid biopsy, has been reported recently. Most such studies have used plasma as a sample; however, whether or not serum can be used as effectively is unclear. We attempted to clarify suitable samples for detecting KRAS mutations in circulating DNA in the blood of pancreatic cancer patients using droplet digital polymerase chain reaction (PCR). Methods DNA was extracted from the tissue, plasma, and serum of 40 pancreatic cancer patients. The presence of KRAS mutations G12D, G12V, and G12R was analyzed by droplet digital PCR. Results The amount of DNA isolated from the serum was much higher than that from plasma (1.0- to 42.0-fold). At least 1 KRAS mutation was observed in 93% of cancer tissues, whereas we detected the mutations in only 48% of the serum and plasma DNA samples. The G12D mutation was the most prevalent of the three mutations, followed by the G12V mutation. The presence of the G12D KRAS mutation in the plasma, serum, or tissue did not correlate to the overall survival; however, the prognosis of the patients with a KRAS mutation at G12V in the plasma or serum was significantly poorer than that of the patients without the mutation (P < 0.01). Conclusions Serum and plasma were found to be good materials for detecting cancer-specific DNA in the peripheral blood and the presence of KRAS mutations in blood-derived DNA may be used as a prognostic biomarker for patients with pancreatic cancer.

Original languageEnglish
Pages (from-to)285-290
Number of pages6
JournalPancreatology
Volume17
Issue number2
DOIs
Publication statusPublished - Mar 1 2017

Fingerprint

Pancreatic Neoplasms
Mutation
DNA
Serum
Neoplasms
Polymerase Chain Reaction
Biomarkers
Biopsy
Survival

Keywords

  • Droplet digital polymerase chain reaction
  • KRAS
  • Liquid biopsy
  • Pancreatic cancer

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Cite this

Utility of serum DNA as a marker for KRAS mutations in pancreatic cancer tissue. / Ako, Soichiro; Nouso, Kazuhiro; Kunugasa, Hideaki; Dohi, Chihiro; Matushita, Hiroshi; Mizukawa, Sho; Muro, Shinichiro; Akimoto, Yutaka; Uchida, Daisuke; Tomoda, Takeshi; Matsumoto, Kazuyuki; Horiguchi, Shigeru; Tsutsumi, Koichiro; Katou, Hironari; Okada, Hiroyuki.

In: Pancreatology, Vol. 17, No. 2, 01.03.2017, p. 285-290.

Research output: Contribution to journalArticle

Ako, Soichiro ; Nouso, Kazuhiro ; Kunugasa, Hideaki ; Dohi, Chihiro ; Matushita, Hiroshi ; Mizukawa, Sho ; Muro, Shinichiro ; Akimoto, Yutaka ; Uchida, Daisuke ; Tomoda, Takeshi ; Matsumoto, Kazuyuki ; Horiguchi, Shigeru ; Tsutsumi, Koichiro ; Katou, Hironari ; Okada, Hiroyuki. / Utility of serum DNA as a marker for KRAS mutations in pancreatic cancer tissue. In: Pancreatology. 2017 ; Vol. 17, No. 2. pp. 285-290.
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abstract = "Background/Objectives The detection of cancer-specific DNA in peripheral blood, known as a liquid biopsy, has been reported recently. Most such studies have used plasma as a sample; however, whether or not serum can be used as effectively is unclear. We attempted to clarify suitable samples for detecting KRAS mutations in circulating DNA in the blood of pancreatic cancer patients using droplet digital polymerase chain reaction (PCR). Methods DNA was extracted from the tissue, plasma, and serum of 40 pancreatic cancer patients. The presence of KRAS mutations G12D, G12V, and G12R was analyzed by droplet digital PCR. Results The amount of DNA isolated from the serum was much higher than that from plasma (1.0- to 42.0-fold). At least 1 KRAS mutation was observed in 93{\%} of cancer tissues, whereas we detected the mutations in only 48{\%} of the serum and plasma DNA samples. The G12D mutation was the most prevalent of the three mutations, followed by the G12V mutation. The presence of the G12D KRAS mutation in the plasma, serum, or tissue did not correlate to the overall survival; however, the prognosis of the patients with a KRAS mutation at G12V in the plasma or serum was significantly poorer than that of the patients without the mutation (P < 0.01). Conclusions Serum and plasma were found to be good materials for detecting cancer-specific DNA in the peripheral blood and the presence of KRAS mutations in blood-derived DNA may be used as a prognostic biomarker for patients with pancreatic cancer.",
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T1 - Utility of serum DNA as a marker for KRAS mutations in pancreatic cancer tissue

AU - Ako, Soichiro

AU - Nouso, Kazuhiro

AU - Kunugasa, Hideaki

AU - Dohi, Chihiro

AU - Matushita, Hiroshi

AU - Mizukawa, Sho

AU - Muro, Shinichiro

AU - Akimoto, Yutaka

AU - Uchida, Daisuke

AU - Tomoda, Takeshi

AU - Matsumoto, Kazuyuki

AU - Horiguchi, Shigeru

AU - Tsutsumi, Koichiro

AU - Katou, Hironari

AU - Okada, Hiroyuki

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Background/Objectives The detection of cancer-specific DNA in peripheral blood, known as a liquid biopsy, has been reported recently. Most such studies have used plasma as a sample; however, whether or not serum can be used as effectively is unclear. We attempted to clarify suitable samples for detecting KRAS mutations in circulating DNA in the blood of pancreatic cancer patients using droplet digital polymerase chain reaction (PCR). Methods DNA was extracted from the tissue, plasma, and serum of 40 pancreatic cancer patients. The presence of KRAS mutations G12D, G12V, and G12R was analyzed by droplet digital PCR. Results The amount of DNA isolated from the serum was much higher than that from plasma (1.0- to 42.0-fold). At least 1 KRAS mutation was observed in 93% of cancer tissues, whereas we detected the mutations in only 48% of the serum and plasma DNA samples. The G12D mutation was the most prevalent of the three mutations, followed by the G12V mutation. The presence of the G12D KRAS mutation in the plasma, serum, or tissue did not correlate to the overall survival; however, the prognosis of the patients with a KRAS mutation at G12V in the plasma or serum was significantly poorer than that of the patients without the mutation (P < 0.01). Conclusions Serum and plasma were found to be good materials for detecting cancer-specific DNA in the peripheral blood and the presence of KRAS mutations in blood-derived DNA may be used as a prognostic biomarker for patients with pancreatic cancer.

AB - Background/Objectives The detection of cancer-specific DNA in peripheral blood, known as a liquid biopsy, has been reported recently. Most such studies have used plasma as a sample; however, whether or not serum can be used as effectively is unclear. We attempted to clarify suitable samples for detecting KRAS mutations in circulating DNA in the blood of pancreatic cancer patients using droplet digital polymerase chain reaction (PCR). Methods DNA was extracted from the tissue, plasma, and serum of 40 pancreatic cancer patients. The presence of KRAS mutations G12D, G12V, and G12R was analyzed by droplet digital PCR. Results The amount of DNA isolated from the serum was much higher than that from plasma (1.0- to 42.0-fold). At least 1 KRAS mutation was observed in 93% of cancer tissues, whereas we detected the mutations in only 48% of the serum and plasma DNA samples. The G12D mutation was the most prevalent of the three mutations, followed by the G12V mutation. The presence of the G12D KRAS mutation in the plasma, serum, or tissue did not correlate to the overall survival; however, the prognosis of the patients with a KRAS mutation at G12V in the plasma or serum was significantly poorer than that of the patients without the mutation (P < 0.01). Conclusions Serum and plasma were found to be good materials for detecting cancer-specific DNA in the peripheral blood and the presence of KRAS mutations in blood-derived DNA may be used as a prognostic biomarker for patients with pancreatic cancer.

KW - Droplet digital polymerase chain reaction

KW - KRAS

KW - Liquid biopsy

KW - Pancreatic cancer

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