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Contreras-Espinosa L, Alcaraz N, De La Rosa-Velázquez IA, et al. Transcriptome Analysis Identifies GATA3-AS1 as a Long Noncoding RNA Associated with Resistance to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients. J Mol Diagn. 2021;23(10):1306-1323doi: 10.1016/j.jmoldx.2021.07.014.
Contreras-Espinosa, L., Alcaraz, N., De La Rosa-Velázquez, I. A., Díaz-Chávez, J., Cabrera-Galeana, P., Rebollar-Vega, R., Reynoso-Noverón, N., Maldonado-Martínez, H. A., González-Barrios, R., Montiel-Manríquez, R., Bautista-Sánchez, D., Castro-Hernández, C., Alvarez-Gomez, R. M., Jiménez-Trejo, F., Tapia-Rodríguez, M., García-Gordillo, J. A., Pérez-Rosas, A., Bargallo-Rocha, E., Arriaga-Canon, C., & Herrera, L. A. (2021). Transcriptome Analysis Identifies GATA3-AS1 as a Long Noncoding RNA Associated with Resistance to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients. The Journal of molecular diagnostics : JMD, 23(10), 1306-1323. https://doi.org/10.1016/j.jmoldx.2021.07.014
Contreras-Espinosa, Laura, et al. "Transcriptome Analysis Identifies GATA3-AS1 as a Long Noncoding RNA Associated with Resistance to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients." The Journal of molecular diagnostics : JMD vol. 23,10 (2021): 1306-1323. doi: https://doi.org/10.1016/j.jmoldx.2021.07.014
Contreras-Espinosa L, Alcaraz N, De La Rosa-Velázquez IA, Díaz-Chávez J, Cabrera-Galeana P, Rebollar-Vega R, Reynoso-Noverón N, Maldonado-Martínez HA, González-Barrios R, Montiel-Manríquez R, Bautista-Sánchez D, Castro-Hernández C, Alvarez-Gomez RM, Jiménez-Trejo F, Tapia-Rodríguez M, García-Gordillo JA, Pérez-Rosas A, Bargallo-Rocha E, Arriaga-Canon C, Herrera LA. Transcriptome Analysis Identifies GATA3-AS1 as a Long Noncoding RNA Associated with Resistance to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients. J Mol Diagn. 2021 Oct;23(10):1306-1323. doi: 10.1016/j.jmoldx.2021.07.014. Epub 2021 Aug 04. PMID: 34358678.
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J Mol Diagn. 2021 Oct;23(10):1306-1323. doi: 10.1016/j.jmoldx.2021.07.014. Epub 2021 Aug 04.

Transcriptome Analysis Identifies GATA3-AS1 as a Long Noncoding RNA Associated with Resistance to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients.

The Journal of molecular diagnostics : JMD

Laura Contreras-Espinosa, Nicolás Alcaraz, Inti A De La Rosa-Velázquez, José Díaz-Chávez, Paula Cabrera-Galeana, Rosa Rebollar-Vega, Nancy Reynoso-Noverón, Héctor A Maldonado-Martínez, Rodrigo González-Barrios, Rogelio Montiel-Manríquez, Diana Bautista-Sánchez, Clementina Castro-Hernández, Rosa M Alvarez-Gomez, Francisco Jiménez-Trejo, Miguel Tapia-Rodríguez, José A García-Gordillo, Augusto Pérez-Rosas, Enrique Bargallo-Rocha, Cristian Arriaga-Canon, Luis A Herrera

Affiliations

  1. Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, National Autonomous University of Mexico (UNAM), Tlalpan, Mexico City, México.
  2. The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
  3. Genomics Laboratory, Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México, Tlalpan, Mexico City, México.
  4. Departamento de Tumores Mamarios, Instituto Nacional de Cancerología, Tlalpan, Mexico City, México.
  5. Centro de Investigación en Prevención, Instituto Nacional de Cancerología, Tlalpan, Mexico City, México.
  6. Patología Molecular e Inmunología, Instituto Nacional de Cancerología, Tlalpan, Mexico City, México.
  7. Clínica de Cáncer Hereditario, Instituto Nacional de Cancerología, Tlalpan, Mexico City, México.
  8. Instituto Nacional de Pediatría, Coyoacán, Mexico City, México.
  9. Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Tercer Circuito Exterior S/N, Ciudad Universitaria, Mexico City, México.
  10. Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, National Autonomous University of Mexico (UNAM), Tlalpan, Mexico City, México. Electronic address: [email protected].
  11. Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, National Autonomous University of Mexico (UNAM), Tlalpan, Mexico City, México; Instituto Nacional de Medicina Genómica, Tlalpan, Mexico City, México. Electronic address: [email protected].

PMID: 34358678 DOI: 10.1016/j.jmoldx.2021.07.014

Abstract

Breast cancer is one of the leading causes of mortality in women worldwide, and neoadjuvant chemotherapy has emerged as an option for the management of locally advanced breast cancer. Extensive efforts have been made to identify new molecular markers to predict the response to neoadjuvant chemotherapy. Transcripts that do not encode proteins, termed long noncoding RNAs (lncRNAs), have been shown to display abnormal expression profiles in different types of cancer, but their role as biomarkers in response to neoadjuvant chemotherapy has not been extensively studied. Herein, lncRNA expression was profiled using RNA sequencing in biopsies from patients who subsequently showed either response or no response to treatment. GATA3-AS1 was overexpressed in the nonresponder group and was the most stable feature when performing selection in multiple random forest models. GATA3-AS1 was experimentally validated by quantitative RT-PCR in an extended group of 68 patients. Expression analysis confirmed that GATA3-AS1 is overexpressed primarily in patients who were nonresponsive to neoadjuvant chemotherapy, with a sensitivity of 92.9% and a specificity of 75.0%. The statistical model was based on luminal B-like patients and adjusted by menopausal status and phenotype (odds ratio, 37.49; 95% CI, 6.74-208.42; P = 0.001); GATA3-AS1 was established as an independent predictor of response. Thus, lncRNA GATA3-AS1 is proposed as a potential predictive biomarker of nonresponse to neoadjuvant chemotherapy.

Copyright © 2021 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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