Comprehensive miRNA profiling of surgically staged endometrial cancer.
OBJECTIVE
We sought to determine a microRNA (miRNA) profile of surgically staged endometrial cancers.


METHODS
RNA was extracted from archival primary endometrial cancers, and an miRNA profile was established using a microarray and confirmed with real-time polymerase chain reaction. Targets of differentially expressed miRNAs were explored using real-time polymerase chain reaction and Western blot in endometrial cell lines.


RESULTS
Endometrial cancer has an miRNA profile distinct from normal endometrium, even in patients with stage IA grade 1 tumors. This miRNA cancer profile was able to correctly assign a specimen as a malignancy with a sensitivity of 92%. Overexpressed miRNAs were predicted to target PTEN, and transfection of cell lines with these miRNAs led to down-regulation of PTEN expression. In advanced disease, an miRNA pattern distinct from early-stage disease was seen, and overexpression of mir-199c predicted improved cancer survival in this population.


CONCLUSIONS
Endometrial cancer has a distinct miRNA profile, and miRNAs can be used as a predictive biomarker.
Cohn
David E
DE
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, OH, USA. David.Cohn@osumc.edu
Fabbri
Muller
M
Valeri
Nicola
N
Alder
Hansjuerg
H
Ivanov
Iouri
I
Liu
Chang-Gong
CG
Croce
Carlo M
CM
Resnick
Kimberly E
KE
D000230:Adenocarcinoma / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D035683:MicroRNAs
Gynecol Oncol. 1983 Feb;15(1):10-7
6822361
Cancer. 2006 Feb 15;106(4):804-11
16400640
Cell Cycle. 2007 Nov 1;6(21):2585-90
17957144
CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49
19474385
Cancer. 2006 Feb 15;106(4):812-9
16400639
Cancer Res. 2007 Sep 15;67(18):8699-707
17875710
Oncogene. 2006 Oct 9;25(46):6197-201
17028599
Int J Cancer. 2009 Mar 15;124(6):1358-65
19065659
Gynecol Oncol. 2008 Aug;110(2):206-15
18499237
JAMA. 2007 May 2;297(17):1901-8
17473300
Eur J Cancer Prev. 2009 Feb;18(1):50-5
19077565
Semin Oncol. 2006 Apr;33(2):167-73
16616063
Nat Protoc. 2008;3(4):563-78
18388938
Cancer Res. 2008 Jul 15;68(14):5619-27
18632614