title: Hypermethylated DNA as a biomarker for colorectal cancer: a systematic review.
abstract: OBJECTIVE
  Improved methods for early detection of colorectal cancer (CRC) are essential for increasing survival. Hypermethylated DNA in blood or stool has been proposed as a biomarker for CRC. Biochemical methods have improved in recent years, and several hypermethylated genes that are sensitive and specific for CRC have been proposed. Articles describing the use of hypermethylated promoter regions in blood or stool as biomarkers for CRC were systematically reviewed.
  
  
  METHODS
  A systematic literature search was performed using the Medline, Web of Science and Embase databases. Studies were included if they analysed hypermethylated genes from stool or blood samples in correlation with CRC. Studies in languages other than English and those based on animal models or cell lines were excluded.
  
  
  RESULTS
  The literature search yielded 74 articles, including 43 addressing blood samples and 31 addressing stool samples. In blood samples, hypermethylated ALX4, FBN2, HLTF, P16, TMEFF1 and VIM were associated with poor prognosis, hypermethylated APC, NEUROG1, RASSF1A, RASSF2A, SDC2, SEPT9, TAC1 and THBD were detected in early stage CRC and hypermethylated P16 and TFPI2 were associated with CRC recurrence. In stool samples, hypermethylated BMP3, PHACTR3, SFRP2, SPG20, TFPI2 and TMEFF2 were associated with early stage CRC.
  
  
  CONCLUSIONS
  Hypermethylation of the promoters of specific genes measured in blood or stool samples could be used as a CRC biomarker and provide prognostic information. The majority of studies, however, include only a few patients with poorly defined control groups. Further studies are therefore needed before hypermethylated DNA can be widely applied as a clinical biomarker for CRC detection and prognosis.
authors.affiliation: Department of Gastrointestinal Surgery and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.|Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: S L
authors.initials: SL
authors.lastname: Rasmussen
authors.affiliation: Section of Molecular Diagnostics, Clinical Biochemistry and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: H B
authors.initials: HB
authors.lastname: Krarup
authors.affiliation: Department of Gastrointestinal Surgery and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: K G
authors.initials: KG
authors.lastname: Sunesen
authors.affiliation: Section of Molecular Diagnostics, Clinical Biochemistry and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: I S
authors.initials: IS
authors.lastname: Pedersen
authors.affiliation: Section of Molecular Diagnostics, Clinical Biochemistry and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: P H
authors.initials: PH
authors.lastname: Madsen
authors.affiliation: Department of Gastrointestinal Surgery and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.|Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: O
authors.initials: O
authors.lastname: Thorlacius-Ussing
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis / Q000097:blood; D055088:Early Detection of Cancer; D005243:Feces / Q000737:chemistry; D006801:Humans
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
keywords: Colorectal cancer; biomarkers; epigenetics; hypermethylation