title: Mitogen-inducible gene-6 expression correlates with survival and is an independent predictor of recurrence in BRAF(V600E) positive papillary thyroid cancers.
abstract: BACKGROUND
  Mitogen-inducible gene-6 (Mig-6) is an immediate early response gene that negatively regulates signaling. EGFR overexpression and activating mutations in MAPK signaling effectors are common events in papillary thyroid cancer (PTC). The purpose of this study was to determine if Mig-6 expression is associated with EGFR expression or surgical outcomes in PTC.
  
  
  METHODS
  We determined Mig-6 transcript levels from a microarray in 19 patients with PTC who underwent thyroidectomy. We established a maximally selected cutoff to discriminate Kaplan-Meier survival estimates. For cross-validation, we performed quantitative RT-PCR on resected well-differentiated PTC from an additional 106 patients.
  
  
  RESULTS
  Mig-6 and EGFR mRNA levels correlated directly (P < .0001). Mig-6 expression above the cutoff of 1.10 (2;-dCt[Mig6-GUS]) was associated with greater survival (P = .008). When this cutoff was applied in the cross-validation, high Mig-6 expression was associated with longer survival (P = .03) and disease-free survival (P = .07). Furthermore, high Mig-6 expression was independently predictive of greater disease-free survival in BRAF(V600E)-positive PTC.
  
  
  CONCLUSIONS
  High Mig-6 expression in PTC is associated with favorable outcomes. Mig-6 is a novel tumor suppressor that may be a candidate for targeted cancer therapeutics in patients with PTC refractory to conventional therapy.
authors.affiliation: Department of Surgery, University of California, San Francisco, San Francisco, Calif, USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Ruan
authors.forename: Robert S
authors.initials: RS
authors.lastname: Warren
authors.forename: Jacob
authors.initials: J
authors.lastname: Moalem
authors.forename: Ki-Wook
authors.initials: KW
authors.lastname: Chung
authors.forename: Ann C
authors.initials: AC
authors.lastname: Griffin
authors.forename: Wen
authors.initials: W
authors.lastname: Shen
authors.forename: Quan-Yang
authors.initials: QY
authors.lastname: Duh
authors.forename: Eric
authors.initials: E
authors.lastname: Nakakura
authors.forename: David B
authors.initials: DB
authors.lastname: Donner
authors.forename: Elham
authors.initials: E
authors.lastname: Khanafshar
authors.forename: Julie
authors.initials: J
authors.lastname: Weng
authors.forename: Orlo H
authors.initials: OH
authors.lastname: Clark
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics*; D000231:Adenocarcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism*; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D013965:Thyroidectomy; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C484017:ERRFI1 protein, human; D025521:Tumor Suppressor Proteins; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf