Mitogen-inducible gene-6 expression correlates with survival and is an independent predictor of recurrence in BRAF(V600E) positive papillary thyroid cancers.
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.
Ruan
Daniel T
DT
Department of Surgery, University of California, San Francisco, San Francisco, Calif, USA.
Warren
Robert S
RS
Moalem
Jacob
J
Chung
Ki-Wook
KW
Griffin
Ann C
AC
Shen
Wen
W
Duh
Quan-Yang
QY
Nakakura
Eric
E
Donner
David B
DB
Khanafshar
Elham
E
Weng
Julie
J
Clark
Orlo H
OH
Kebebew
Electron
E
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
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