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Identification of a novel diagnostic gene expression signature to discriminate uterine leiomyoma from leiomyosarcoma.
Exp Mol Pathol. 2019 10; 110:104284.EM

Abstract

Leiomyosarcomas are rare, aggressive tumors, which exhibit a poor prognosis regardless of stage. Pre-operative diagnosis can be difficult as leiomyosarcoma can mimic features of the more common, benign uterine leiomyoma. The goal of this study was to identify specific molecular markers to discriminate between uterine leiomyosarcomas and leiomyomas to facilitate timely, accurate diagnosis and treatment. Gene expression profiles of three leiomyosarcomas, leiomyomas, and normal myometrial tissue samples were analyzed using the Affymetrix Human Gene 1.0 ST Array. GC-robust multiarray average calculation and ANOVA statistical testing were used to identify differentially expressed genes. Sixty genes, with functional roles in tumor progression or suppression, exhibited divergent expression profiles in leiomyosarcomas and leiomyomas, compared to normal myometrium. Differential RNA and protein levels of seven genes, with the most discriminatory expression patterns, were confirmed by RTPCR and immunohistochemistry in an additional 10 leiomyosarcoma and 20 leiomyoma independent samples. CHI3L1, MELK, PRC1, TOP2A, and TPX2 were overexpressed in leiomyosarcomas, while HPGD and TES were overexpressed in leiomyomas. Distinguishing leiomyosarcomas from leiomyomas represents a diagnostic challenge, particularly in the context of minimally invasive surgery. The unique gene expression signatures identified in this study may accurately differentiate between these tumor types at the earliest stage and provides potential prognostic factors and novel therapeutic targets for the treatment of leiomyosarcoma.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, Division of Reproductive Sciences, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.Department of Obstetrics and Gynecology, Division of Reproductive Sciences, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA; Department of Obstetrics and Gynecology, Division Gynecologic Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.Department of Obstetrics and Gynecology, Division of Reproductive Sciences, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.Department of Obstetrics and Gynecology, Division of Reproductive Sciences, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA; Department of Obstetrics and Gynecology, Division Gynecologic Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.Department of Obstetrics and Gynecology, Division Gynecologic Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.Department of Obstetrics and Gynecology, Division of Reproductive Sciences, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA. Electronic address: Andy.Bradford@ucdenver.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

31301306

Citation

Adams, Crystal L., et al. "Identification of a Novel Diagnostic Gene Expression Signature to Discriminate Uterine Leiomyoma From Leiomyosarcoma." Experimental and Molecular Pathology, vol. 110, 2019, p. 104284.
Adams CL, Dimitrova I, Post MD, et al. Identification of a novel diagnostic gene expression signature to discriminate uterine leiomyoma from leiomyosarcoma. Exp Mol Pathol. 2019;110:104284.
Adams, C. L., Dimitrova, I., Post, M. D., Gibson, L., Spillman, M. A., Behbakht, K., & Bradford, A. P. (2019). Identification of a novel diagnostic gene expression signature to discriminate uterine leiomyoma from leiomyosarcoma. Experimental and Molecular Pathology, 110, 104284. https://doi.org/10.1016/j.yexmp.2019.104284
Adams CL, et al. Identification of a Novel Diagnostic Gene Expression Signature to Discriminate Uterine Leiomyoma From Leiomyosarcoma. Exp Mol Pathol. 2019;110:104284. PubMed PMID: 31301306.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of a novel diagnostic gene expression signature to discriminate uterine leiomyoma from leiomyosarcoma. AU - Adams,Crystal L, AU - Dimitrova,Irina, AU - Post,Miriam D, AU - Gibson,Lacey, AU - Spillman,Monique A, AU - Behbakht,Kian, AU - Bradford,Andrew P, Y1 - 2019/07/10/ PY - 2019/04/02/received PY - 2019/06/03/revised PY - 2019/07/09/accepted PY - 2019/7/14/pubmed PY - 2020/2/26/medline PY - 2019/7/14/entrez KW - Diagnosis KW - Gene expression KW - Leiomyoma KW - Leiomyosarcoma KW - Molecular profiling SP - 104284 EP - 104284 JF - Experimental and molecular pathology JO - Exp. Mol. Pathol. VL - 110 N2 - Leiomyosarcomas are rare, aggressive tumors, which exhibit a poor prognosis regardless of stage. Pre-operative diagnosis can be difficult as leiomyosarcoma can mimic features of the more common, benign uterine leiomyoma. The goal of this study was to identify specific molecular markers to discriminate between uterine leiomyosarcomas and leiomyomas to facilitate timely, accurate diagnosis and treatment. Gene expression profiles of three leiomyosarcomas, leiomyomas, and normal myometrial tissue samples were analyzed using the Affymetrix Human Gene 1.0 ST Array. GC-robust multiarray average calculation and ANOVA statistical testing were used to identify differentially expressed genes. Sixty genes, with functional roles in tumor progression or suppression, exhibited divergent expression profiles in leiomyosarcomas and leiomyomas, compared to normal myometrium. Differential RNA and protein levels of seven genes, with the most discriminatory expression patterns, were confirmed by RTPCR and immunohistochemistry in an additional 10 leiomyosarcoma and 20 leiomyoma independent samples. CHI3L1, MELK, PRC1, TOP2A, and TPX2 were overexpressed in leiomyosarcomas, while HPGD and TES were overexpressed in leiomyomas. Distinguishing leiomyosarcomas from leiomyomas represents a diagnostic challenge, particularly in the context of minimally invasive surgery. The unique gene expression signatures identified in this study may accurately differentiate between these tumor types at the earliest stage and provides potential prognostic factors and novel therapeutic targets for the treatment of leiomyosarcoma. SN - 1096-0945 UR - https://www.unboundmedicine.com/medline/citation/31301306/Identification_of_a_novel_diagnostic_gene_expression_signature_to_discriminate_uterine_leiomyoma_from_leiomyosarcoma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4800(19)30243-6 DB - PRIME DP - Unbound Medicine ER -