title: Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care.
abstract: Circulating cell-free DNA (ccfDNA) is a valuable source of tumor material obtained from a simple blood sampling that enables noninvasive analysis of the tumor genome. Our goal was to carry out a multiparametric analysis of ccfDNA and evaluate its prognostic value by investigating the overall survival (OS) of 97 metastatic colorectal cancer patients (mCRC).
  
  
  
  Qualitative parameters (determination of the main KRAS exon2 and BRAF V600E mutations) and quantitative parameters (total ccfDNA concentration, mutant ccfDNA concentration, the proportion of mutant ccfDNA, and ccfDNA integrity index) were determined simultaneously in a single run using a unique Q-PCR multimarker approach (100% success rate).
  
  
  
  The median follow-up time was 36 months and median OS was 22 months. Patients showing high ccfDNA levels had significantly shorter OS (18.07 months vs. 28.5 months, P = 0.0087). Moreover, multivariate analysis revealed that a high ccfDNA level is an independent prognostic factor (P = 0.034). All ccfDNA parameters were of prognostic interest: patients with higher levels of mutant ccfDNA and higher mutation loads for the detected mutations had shorter OS (P = 0.0089 and P = 0.05, respectively). In addition, the level of ccfDNA fragmentation correlated positively with decreased OS in the exclusive KRAS/BRAF-mutant cohort of patients (P = 0.0052) and appeared as a strong independent prognostic factor (P = 0.0072), whereas it was not significant in the exclusive KRAS/BRAF WT cohort of patients (P = 0.67).
  
  
  
  Our data provide for the first time qualitative and quantitative evidence in favor of multiparametric ccfDNA analysis in mCRC patients for prognostic assessment. Clin Cancer Res; 22(12); 3067-77. ©2016 AACR.
authors: IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France. INSERM, U1194, Montpellier, France. Université de Montpellier, Montpellier, France. Institut régional du Cancer de Montpellier, Montpellier, France.
authors: Safia
authors: S
authors: El Messaoudi
authors: IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France. INSERM, U1194, Montpellier, France. Université de Montpellier, Montpellier, France. Institut régional du Cancer de Montpellier, Montpellier, France.
authors: Florent
authors: F
authors: Mouliere
authors: IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France. INSERM, U1194, Montpellier, France. Université de Montpellier, Montpellier, France. Institut régional du Cancer de Montpellier, Montpellier, France.
authors: Stanislas
authors: S
authors: Du Manoir
authors: IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France. INSERM, U1194, Montpellier, France. Université de Montpellier, Montpellier, France. Institut régional du Cancer de Montpellier, Montpellier, France. Unité de Biométrie Institut régional du Cancer de Montpellier, Montpellier, France.
authors: Caroline
authors: C
authors: Bascoul-Mollevi
authors: Centre Hospitalier Universitaire de Clermont-Ferrand, Service de Chirurgie Digestive Unité d'Oncologie Digestive, UMR Unité Inserm/Université d'Auvergne U1071, Clermont-Ferrand, France.
authors: Brigitte
authors: B
authors: Gillet
authors: Centre Hospitalier Universitaire de Limoges, Service de Chirurgie Digestive, Centre d'Investigation Clinique, INSERM 0801, Limoges, France.
authors: Michelle
authors: M
authors: Nouaille
authors: Service de Recherche Clinique, Institut régional du Cancer de Montpellier, Montpellier, France.
authors: Catherine
authors: C
authors: Fiess
authors: IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France. INSERM, U1194, Montpellier, France. Université de Montpellier, Montpellier, France. Institut régional du Cancer de Montpellier, Montpellier, France.
authors: Evelyne
authors: E
authors: Crapez
authors: IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France. INSERM, U1194, Montpellier, France. Université de Montpellier, Montpellier, France. Institut régional du Cancer de Montpellier, Montpellier, France. Service d'Anatomo-Pathologie, Institut régional du Cancer de Montpellier, Montpellier, France.
authors: Frederic
authors: F
authors: Bibeau
authors: IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France. INSERM, U1194, Montpellier, France. Université de Montpellier, Montpellier, France. Institut régional du Cancer de Montpellier, Montpellier, France.
authors: Charles
authors: C
authors: Theillet
authors: IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France. INSERM, U1194, Montpellier, France. Université de Montpellier, Montpellier, France. Institut régional du Cancer de Montpellier, Montpellier, France. Service de Chirurgie Digestive, Institut régional du Cancer de Montpellier, Montpellier, France.
authors: Thibault
authors: T
authors: Mazard
authors: Centre Hospitalier Universitaire de Clermont-Ferrand, Service de Chirurgie Digestive Unité d'Oncologie Digestive, UMR Unité Inserm/Université d'Auvergne U1071, Clermont-Ferrand, France.
authors: Denis
authors: D
authors: Pezet
authors: Centre Hospitalier Universitaire de Limoges, Service de Chirurgie Digestive, Centre d'Investigation Clinique, INSERM 0801, Limoges, France.
authors: Muriel
authors: M
authors: Mathonnet
authors: IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France. INSERM, U1194, Montpellier, France. Université de Montpellier, Montpellier, France. Institut régional du Cancer de Montpellier, Montpellier, France. Service de Chirurgie Digestive, Institut régional du Cancer de Montpellier, Montpellier, France.
authors: Marc
authors: M
authors: Ychou
authors: IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France. INSERM, U1194, Montpellier, France. Université de Montpellier, Montpellier, France. Institut régional du Cancer de Montpellier, Montpellier, France. alain.thierry@inserm.fr.
authors: Alain R
authors: AR
authors: Thierry
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D000073888:Cell-Free Nucleic Acids / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000097:blood*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D000073888:Cell-Free Nucleic Acids; D004273:DNA, Neoplasm; C117307:KRAS protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)