title: The prognostic value of simultaneous tumor and serum RAS/RAF mutations in localized colon cancer.
abstract: The impact of RAS/RAF mutations in localized colon cancer needs clarification. Based on analysis of tumor-specific DNA, this study aimed at elucidating the prognostic influence of mutational status in tumor and serum using an extended panel of mutations. The study retrospectively included 294 patients with curatively resected stage I-III adenocarcinoma of the colon. Mutations in tumor and serum were determined at time of surgery. Analyses were performed with droplet digital PCR technology. Hazard ratio (HR) for the association between mutational status and survival was estimated in multivariate analysis taking known prognostic factors into account. Mutational status in tumor did not on its own have significant prognostic impact (P = 0.22). Patients with a RAS mutation simultaneously in tumor and serum had a significantly worse prognosis, overall survival (OS) (HR = 2.30, 95% CI = 1.27-4.15, P = 0.0057), and disease-free survival (DFS) (HR = 2.18, 95%CI = 1.26-3.77, P = 0.0053). BRAF mutation in the serum and proficient mismatch repair (pMMR) protein in tumor also indicated significantly worse prognosis, OS (HR = 3.45, 95% CI = 1.52-7.85, P = 0.0032) and DFS (HR = 3.61, 95% CI = 1.70-7.67, P = 0.0008). In conclusion, RAS mutations in serum, and BRAF mutation in serum combined with pMMR in tumor were strong independent prognostic factors in patients with RAS/RAF mutated tumors.
authors.affiliation: Danish Colorectal Cancer Center South, Vejle Hospital, Beridderbakken 4, Vejle, DK-7100, Denmark.|Institute of Regional Health Research, University of Southern Denmark, Winsløwparken 19-3, Odense, DK-5000, Denmark.
authors.forename: Caroline Emilie B
authors.identifier: http://orcid.org/0000-0003-4481-6274
authors.initials: CEB
authors.lastname: Thomsen
authors.affiliation: Danish Colorectal Cancer Center South, Vejle Hospital, Beridderbakken 4, Vejle, DK-7100, Denmark.|Department of Radiation Oncology, Rigshospitalet, Blegdamsvej 9, Copenhagen East, DK-2100, Denmark.|Leeds Institute of Cancer and Pathology, University of Leeds and St James's University Hospital, Leeds, United Kingdom.
authors.forename: Ane Lindegaard
authors.initials: AL
authors.lastname: Appelt
authors.affiliation: Danish Colorectal Cancer Center South, Vejle Hospital, Beridderbakken 4, Vejle, DK-7100, Denmark.
authors.forename: Rikke Fredslund
authors.identifier: http://orcid.org/0000-0002-5894-7745
authors.initials: RF
authors.lastname: Andersen
authors.affiliation: Danish Colorectal Cancer Center South, Vejle Hospital, Beridderbakken 4, Vejle, DK-7100, Denmark.|Institute of Regional Health Research, University of Southern Denmark, Winsløwparken 19-3, Odense, DK-5000, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Lindebjerg
authors.affiliation: Danish Colorectal Cancer Center South, Vejle Hospital, Beridderbakken 4, Vejle, DK-7100, Denmark.|Institute of Regional Health Research, University of Southern Denmark, Winsløwparken 19-3, Odense, DK-5000, Denmark.
authors.forename: Lars Henrik
authors.identifier: http://orcid.org/0000-0002-0020-1537
authors.initials: LH
authors.lastname: Jensen
authors.affiliation: Danish Colorectal Cancer Center South, Vejle Hospital, Beridderbakken 4, Vejle, DK-7100, Denmark.|Institute of Regional Health Research, University of Southern Denmark, Winsløwparken 19-3, Odense, DK-5000, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Jakobsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000097:blood; D012189:Retrospective Studies; D016019:Survival Analysis; D048490:raf Kinases / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D018631:ras Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048490:raf Kinases; D018631:ras Proteins
keywords: 
  BRAF
  ; 
  RAS
  ; colon cancer; liquid biopsy; serum