title: Identification of SOCS2 and SOCS6 as biomarkers in human colorectal cancer.
abstract: BACKGROUND
  Over the past years, some members of the family of suppressor of cytokine signalling (SOCS) proteins have emerged as potential tumour suppressors. This study aimed at investigating the clinical significance of SOCS proteins in colorectal carcinoma (CRC).
  
  
  METHODS
  We integrated publicly available microarray expression data on CRC in humans, analysed the expression pattern of SOCSs and assessed the predictive power of SOCS2 and SOCS6 for diagnostic purposes by generating receiver operating characteristic curves. Using laser microdissected patient material we assessed SOCS expression on RNA and protein levels as well as their methylation status in an independent CRC patient cohort. Finally, we investigated the prognostic value of SOCS2 and SOCS6.
  
  
  RESULTS
  The meta-analysis as well as the independent patient cohort analysis reveal a stage-independent downregulation of SOCS2 and SOCS6 and identify both molecules as diagnostic biomarkers for CRC. We demonstrate a different methylation pattern within the SOCS2 promoter between tumour tissue and normal control tissue in 25% of CRC patients. Furthermore, early CRC stage patients with low expression of SOCS2 display significantly shorter disease-free survival.
  
  
  CONCLUSIONS
  Our data offers evidence that SOCS2 and SOCS6 levels are reduced in CRC and may serve as diagnostic biomarkers for CRC patients.
authors.affiliation: Molecular Disease Mechanisms Group, Life Sciences Research Unit, University of Luxembourg, 162A avenue de la Faïencerie, L-1511 Luxembourg, Luxembourg.
authors.forename: E
authors.initials: E
authors.lastname: Letellier
authors.affiliation: Molecular Disease Mechanisms Group, Life Sciences Research Unit, University of Luxembourg, 162A avenue de la Faïencerie, L-1511 Luxembourg, Luxembourg.
authors.forename: M
authors.initials: M
authors.lastname: Schmitz
authors.affiliation: Molecular Disease Mechanisms Group, Life Sciences Research Unit, University of Luxembourg, 162A avenue de la Faïencerie, L-1511 Luxembourg, Luxembourg.
authors.forename: K
authors.initials: K
authors.lastname: Baig
authors.affiliation: Molecular Disease Mechanisms Group, Life Sciences Research Unit, University of Luxembourg, 162A avenue de la Faïencerie, L-1511 Luxembourg, Luxembourg.
authors.forename: N
authors.initials: N
authors.lastname: Beaume
authors.affiliation: 1] Molecular Disease Mechanisms Group, Life Sciences Research Unit, University of Luxembourg, 162A avenue de la Faïencerie, L-1511 Luxembourg, Luxembourg [2] Laboratoire National de la Santé, 42 r. du Laboratoire, 1911 Luxembourg, Luxembourg.
authors.forename: C
authors.initials: C
authors.lastname: Schwartz
authors.affiliation: Integrated Biobank of Luxembourg, 6 rue Nicolas Ernest Barblé, L-1210 Luxembourg, Luxembourg.
authors.forename: S
authors.initials: S
authors.lastname: Frasquilho
authors.affiliation: Integrated Biobank of Luxembourg, 6 rue Nicolas Ernest Barblé, L-1210 Luxembourg, Luxembourg.
authors.forename: L
authors.initials: L
authors.lastname: Antunes
authors.affiliation: Integrated Biobank of Luxembourg, 6 rue Nicolas Ernest Barblé, L-1210 Luxembourg, Luxembourg.
authors.forename: N
authors.initials: N
authors.lastname: Marcon
authors.affiliation: Genomics Research Unit, Centre de Recherche Public de la Santé Luxembourg 1 A-B, rue Thomas Edison, L-1445 Strassen, Luxembourg.
authors.forename: P V
authors.initials: PV
authors.lastname: Nazarov
authors.affiliation: Genomics Research Unit, Centre de Recherche Public de la Santé Luxembourg 1 A-B, rue Thomas Edison, L-1445 Strassen, Luxembourg.
authors.forename: L
authors.initials: L
authors.lastname: Vallar
authors.affiliation: Laboratoire National de la Santé, 42 r. du Laboratoire, 1911 Luxembourg, Luxembourg.
authors.forename: J
authors.initials: J
authors.lastname: Even
authors.affiliation: Molecular Disease Mechanisms Group, Life Sciences Research Unit, University of Luxembourg, 162A avenue de la Faïencerie, L-1511 Luxembourg, Luxembourg.
authors.forename: S
authors.initials: S
authors.lastname: Haan
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D019175:DNA Methylation; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C106643:SOCS2 protein, human; C473085:SOCS6 protein, human; D050826:Suppressor of Cytokine Signaling Proteins