TIMP1 and SERPIN-A overexpression and TFF3 and CRABP1 underexpression as biomarkers for papillary thyroid carcinoma.
BACKGROUND
No molecular pathways or specific genes are consistently associated with sporadic cases of papillary thyroid carcinoma (PTC), despite that it is the most common thyroid malignancy. Nodular goiter is an enlargement of the thyroid that is a compensatory response to a perturbation in normal thyroid homeostasis. It has been disputed in the literature that patients presenting with goiter have a higher incidence of PTC. The identification of molecular events that are common to both goiter and PTC could explain the overlap of these two disorders.


METHODS
We used high-density oligonuleotide arrays to perform molecular profiling of PTC and nodular goiter with paired normal samples.


RESULTS
Specifically, increased expression of SERPIN-A (proteinase inhibitor-alpha antitrypsin) and TIMP 1 (tissue inhibitor of metalloproteinase 1) identified these as candidate molecular biomarkers for PTC. Decreases in the CRABP1 (cellular retinoic acid binding protein 1) and TFF3 (trefoil factor 3) expression levels identified these as candidate molecular biomarkers as well. The same analysis was performed to identify genes showing specific alterations in goiter tissues.


CONCLUSIONS
This is the first report to our knowledge that compares the gene expression profiles of PTC and goiter. Our results suggest that PTC and goiter share very limited overlap in transcript expression.
Hawthorn
Lesleyann
L
Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263, USA. lesleyann.hawthorn@roswellpark.org
Stein
Leighton
L
Varma
Ram
R
Wiseman
Samuel
S
Loree
Thom
T
Tan
DongFeng
D
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001707:Biopsy, Needle; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D000071165:Trefoil Factor-3; D000514:alpha 1-Antichymotrypsin / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D010455:Peptides; D018168:Receptors, Retinoic Acid; C082495:TFF3 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D000071165:Trefoil Factor-3; D000514:alpha 1-Antichymotrypsin; C082927:retinoic acid binding protein I, cellular