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Comprehensive miRNA profiling of surgically staged endometrial cancer

Published:April 19, 2010DOI:https://doi.org/10.1016/j.ajog.2010.02.051

      Objective

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

      Study Design

      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.

      Conclusion

      Endometrial cancer has a distinct miRNA profile, and miRNAs can be used as a predictive biomarker.

      Key words

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      References

        • Jemal A.
        • Siegel R.
        • Ward E.
        • Hao Y.
        • Xu J.
        • Thun M.J.
        Cancer statistics, 2009.
        CA Cancer J Clin. 2009; 59: 225-249
        • Bokhman J.V.
        Two pathogenetic types of endometrial carcinoma.
        Gynecol Oncol. 1983; 15: 10-17
        • Jannot G.
        • Simard M.J.
        Tumor-related microRNAs functions in Caenorhabditis elegans.
        Oncogene. 2006; 25: 6197-6201
        • Bloomston M.
        • Frankel W.L.
        • Petrocca F.
        • et al.
        MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis.
        JAMA. 2007; 297: 1901-1908
        • Iorio M.V.
        • Visone R.
        • Di Leva G.
        • et al.
        MicroRNA signatures in human ovarian cancer.
        Cancer Res. 2007; 67: 8699-8707
        • Calin G.A.
        • Croce C.M.
        Genomics of chronic lymphocytic leukemia microRNAs as new players with clinical significance.
        Semin Oncol. 2006; 33: 167-173
        • Boren T.
        • Xiong Y.
        • Hakam A.
        • et al.
        MicroRNAs and their target messenger RNAs associated with endometrial carcinogenesis.
        Gynecol Oncol. 2008; 110: 206-215
        • Daikoku T.
        • Hirota Y.
        • Tranguch S.
        • et al.
        Conditional loss of uterine Pten unfailingly and rapidly induces endometrial cancer in mice.
        Cancer Res. 2008; 68: 5619-5627
        • Chung T.K.
        • Cheung T.H.
        • Huen N.Y.
        • et al.
        Dysregulated microRNAs and their predicted targets associated with endometrioid endometrial adenocarcinoma in Hong Kong women.
        Int J Cancer. 2009; 124: 1358-1365
        • Wu W.
        • Lin Z.
        • Zhuang Z.
        • Liang X.
        Expression profile of mammalian microRNAs in endometrioid adenocarcinoma.
        Eur J Cancer Prev. 2009; 18: 50-55
        • Liu C.G.
        • Calin G.A.
        • Volinia S.
        • Croce C.M.
        MicroRNA expression profiling using microarrays.
        Nat Protoc. 2008; 3: 563-578
        • Park S.M.
        • Shell S.
        • Radjabi A.R.
        • et al.
        Let-7 prevents early cancer progression by suppressing expression of the embryonic gene HMGA2.
        Cell Cycle. 2007; 6: 2585-2590
        • Trimble C.L.
        • Kauderer J.
        • Zaino R.
        • et al.
        Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study.
        Cancer. 2006; 106: 812-819
        • Zaino R.J.
        • Kauderer J.
        • Trimble C.L.
        • et al.
        Reproducibility of the diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study.
        Cancer. 2006; 106: 804-811