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Identification of early stage recurrence endometrial cancer biomarkers using bioinformatics tools

  • Authors:
    • María José Besso
    • Luciana Montivero
    • Ezequiel Lacunza
    • María Cecilia Argibay
    • Martín Abba
    • Laura Inés Furlong
    • Eva Colas
    • Antonio Gil‑Moreno
    • Jaume Reventos
    • Ricardo Bello
    • Mónica Hebe Vazquez‑Levin
  • View Affiliations / Copyright

    Affiliations: Laboratorio de Estudios de Interacción Celular en Reproducción y Cáncer, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina (CONICET)‑Fundación IBYME (FIBYME), Ciudad Autónoma de Buenos Aires 1428ADN, Argentina, Centro de Investigaciones Inmunológicas, Básicas y Aplicadas, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Buenos Aires 1900, Argentina, Integrative Biomedical Informatics Group, Research Programme on Biomedical Informatics, Hospital del Mar Medical Research Institute, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08002 Barcelona, Spain, Biomedical Research Group in Gynecology, Vall d´Hebron Research Institute (VHIR), Universitat Autónoma de Barcelona, CIBERONC, 08035 Barcelona, Spain, Departamento de Metodología, Estadística y Matemática, Universidad de Tres de Febrero, Sáenz Peña, Buenos Aires B1674AHF, Argentina
    Copyright: © Besso et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 873-886
    |
    Published online on: June 16, 2020
       https://doi.org/10.3892/or.2020.7648
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Abstract

Endometrial cancer (EC) is the sixth most common cancer in women worldwide. Early diagnosis is critical in recurrent EC management. The present study aimed to identify biomarkers of EC early recurrence using a workflow that combined text and data mining databases (DisGeNET, Gene Expression Omnibus), a prioritization algorithm to select a set of putative candidates (ToppGene), protein‑protein interaction network analyses (Search Tool for the Retrieval of Interacting Genes, cytoHubba), association analysis of selected genes with clinicopathological parameters, and survival analysis (Kaplan‑Meier and Cox proportional hazard ratio analyses) using a The Cancer Genome Atlas cohort. A total of 10 genes were identified, among which the targeting protein for Xklp2 (TPX2) was the most promising independent prognostic biomarker in stage I EC. TPX2 expression (mRNA and protein) was higher (P<0.0001 and P<0.001, respectively) in ETS variant transcription factor 5‑overexpressing Hec1a and Ishikawa cells, a previously reported cell model of aggressive stage I EC. In EC biopsies, TPX2 mRNA expression levels were higher (P<0.05) in high grade tumors (grade 3) compared with grade 1‑2 tumors (P<0.05), in tumors with deep myometrial invasion (>50% compared with <50%; P<0.01), and in intermediate‑high recurrence risk tumors compared with low‑risk tumors (P<0.05). Further validation studies in larger and independent EC cohorts will contribute to confirm the prognostic value of TPX2.
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Besso MJ, Montivero L, Lacunza E, Argibay MC, Abba M, Furlong LI, Colas E, Gil‑Moreno A, Reventos J, Bello R, Bello R, et al: Identification of early stage recurrence endometrial cancer biomarkers using bioinformatics tools. Oncol Rep 44: 873-886, 2020.
APA
Besso, M.J., Montivero, L., Lacunza, E., Argibay, M.C., Abba, M., Furlong, L.I. ... Vazquez‑Levin, M.H. (2020). Identification of early stage recurrence endometrial cancer biomarkers using bioinformatics tools. Oncology Reports, 44, 873-886. https://doi.org/10.3892/or.2020.7648
MLA
Besso, M. J., Montivero, L., Lacunza, E., Argibay, M. C., Abba, M., Furlong, L. I., Colas, E., Gil‑Moreno, A., Reventos, J., Bello, R., Vazquez‑Levin, M. H."Identification of early stage recurrence endometrial cancer biomarkers using bioinformatics tools". Oncology Reports 44.3 (2020): 873-886.
Chicago
Besso, M. J., Montivero, L., Lacunza, E., Argibay, M. C., Abba, M., Furlong, L. I., Colas, E., Gil‑Moreno, A., Reventos, J., Bello, R., Vazquez‑Levin, M. H."Identification of early stage recurrence endometrial cancer biomarkers using bioinformatics tools". Oncology Reports 44, no. 3 (2020): 873-886. https://doi.org/10.3892/or.2020.7648
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Spandidos Publications style
Besso MJ, Montivero L, Lacunza E, Argibay MC, Abba M, Furlong LI, Colas E, Gil‑Moreno A, Reventos J, Bello R, Bello R, et al: Identification of early stage recurrence endometrial cancer biomarkers using bioinformatics tools. Oncol Rep 44: 873-886, 2020.
APA
Besso, M.J., Montivero, L., Lacunza, E., Argibay, M.C., Abba, M., Furlong, L.I. ... Vazquez‑Levin, M.H. (2020). Identification of early stage recurrence endometrial cancer biomarkers using bioinformatics tools. Oncology Reports, 44, 873-886. https://doi.org/10.3892/or.2020.7648
MLA
Besso, M. J., Montivero, L., Lacunza, E., Argibay, M. C., Abba, M., Furlong, L. I., Colas, E., Gil‑Moreno, A., Reventos, J., Bello, R., Vazquez‑Levin, M. H."Identification of early stage recurrence endometrial cancer biomarkers using bioinformatics tools". Oncology Reports 44.3 (2020): 873-886.
Chicago
Besso, M. J., Montivero, L., Lacunza, E., Argibay, M. C., Abba, M., Furlong, L. I., Colas, E., Gil‑Moreno, A., Reventos, J., Bello, R., Vazquez‑Levin, M. H."Identification of early stage recurrence endometrial cancer biomarkers using bioinformatics tools". Oncology Reports 44, no. 3 (2020): 873-886. https://doi.org/10.3892/or.2020.7648
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