Min Kyeong Kim1, Sang Myung Woo2, Boram Park3, Kyong-Ah Yoon4, Yun-Hee Kim5,6, Jungnam Joo3, Woo Jin Lee2, Sung-Sik Han2, Sang-Jae Park2, Sun-Young Kong7,5,8. 1. Translational Cancer Research Branch, Division of Translational Science, National Cancer Center, Goyang, Korea. 2. Center for Liver Cancer, National Cancer Center, Goyang, Korea. 3. Biometrics Research Branch, Division of Cancer Epidemiology and Management, National Cancer Center, Goyang, Korea. 4. College of Veterinary Medicine, Konkuk University, Seoul, Korea. 5. Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea. 6. Molecular Imaging Branch, Division of Convergence Technology, National Cancer Center, Goyang, Korea. 7. Translational Cancer Research Branch, Division of Translational Science, National Cancer Center, Goyang, Korea; ksy@ncc.re.kr. 8. Department of Laboratory Medicine, Center for Diagnostic Oncology, National Cancer Center, Goyang, Korea.
Abstract
BACKGROUND: Cell-free DNA (cfDNA) is known to provide potential biomarkers for predicting clinical outcome, but its value in pancreatic ductal adenocarcinoma (PDAC) has not been fully evaluated. The aim of this study was to evaluate the clinical applicability of quantitative analysis of multiplex KRAS mutations in cell-free DNA from patients with PDAC. METHODS: A total of 106 patients with PDAC were enrolled in this prospective study. The concentration and fraction of KRAS mutations were determined through multiplex detection of KRAS mutations in plasma samples by use of a droplet digital PCR kit (Bio-Rad). RESULTS: KRAS mutations were detected in 96.1% of tissue samples. Eighty patients (80.5%) harbored KRAS mutations in cfDNA, with a median KRAS mutation concentration of 0.165 copies/μL and a median fractional abundance of 0.415%. Multivariable analyses demonstrated that the KRAS mutation concentration [hazard ratio (HR), 2.08; 95% CI, 1.20-3.63] and KRAS fraction (HR, 1.73; 95% CI, 1.02-2.95) were significant factors for progression-free survival. KRAS mutation concentration (HR, 1.97; 95% CI, 1.05-3.67) also had prognostic implications for overall survival. Subgroup analyses showed that KRAS mutation concentration and fractional abundance significantly affected progression-free survival in resectable PDAC (P = 0.016). Moreover, when combined with the cancer biomarker CA19-9, the KRAS mutation concentration in cfDNA showed additive benefits for the prediction of overall survival. CONCLUSIONS: This study demonstrates that multiplex detection of KRAS mutations in plasma cfDNA is clinically relevant, providing a potential candidate biomarker for prognosis of PDAC.
BACKGROUND: Cell-free DNA (cfDNA) is known to provide potential biomarkers for predicting clinical outcome, but its value in pancreatic ductal adenocarcinoma (PDAC) has not been fully evaluated. The aim of this study was to evaluate the clinical applicability of quantitative analysis of multiplex KRAS mutations in cell-free DNA from patients with PDAC. METHODS: A total of 106 patients with PDAC were enrolled in this prospective study. The concentration and fraction of KRAS mutations were determined through multiplex detection of KRAS mutations in plasma samples by use of a droplet digital PCR kit (Bio-Rad). RESULTS:KRAS mutations were detected in 96.1% of tissue samples. Eighty patients (80.5%) harbored KRAS mutations in cfDNA, with a median KRAS mutation concentration of 0.165 copies/μL and a median fractional abundance of 0.415%. Multivariable analyses demonstrated that the KRAS mutation concentration [hazard ratio (HR), 2.08; 95% CI, 1.20-3.63] and KRAS fraction (HR, 1.73; 95% CI, 1.02-2.95) were significant factors for progression-free survival. KRAS mutation concentration (HR, 1.97; 95% CI, 1.05-3.67) also had prognostic implications for overall survival. Subgroup analyses showed that KRAS mutation concentration and fractional abundance significantly affected progression-free survival in resectable PDAC (P = 0.016). Moreover, when combined with the cancer biomarker CA19-9, the KRAS mutation concentration in cfDNA showed additive benefits for the prediction of overall survival. CONCLUSIONS: This study demonstrates that multiplex detection of KRAS mutations in plasma cfDNA is clinically relevant, providing a potential candidate biomarker for prognosis of PDAC.
Authors: Sun Il Choi; A-Ra Jeon; Min Kyeong Kim; Yu-Sun Lee; Ji Eun Im; Jung-Wook Koh; Sung-Sik Han; Sun-Young Kong; Kyong-Ah Yoon; Young-Hwan Koh; Ju Hee Lee; Woo Jin Lee; Sang-Jae Park; En Kyung Hong; Sang Myung Woo; Yun-Hee Kim Journal: Front Oncol Date: 2019-09-13 Impact factor: 6.244
Authors: Marin Strijker; Eline C Soer; Matteo de Pastena; Aafke Creemers; Alberto Balduzzi; Jamie J Beagan; Olivier R Busch; Otto M van Delden; Hans Halfwerk; Jeanin E van Hooft; Krijn P van Lienden; Giovanni Marchegiani; Sybren L Meijer; Carel J van Noesel; Roy J Reinten; Eva Roos; Sandor Schokker; Joanne Verheij; Marc J van de Vijver; Cynthia Waasdorp; Johanna W Wilmink; Bauke Ylstra; Marc G Besselink; Maarten F Bijlsma; Frederike Dijk; Hanneke W van Laarhoven Journal: Int J Cancer Date: 2019-08-13 Impact factor: 7.396