Transcriptome Analysis Identifies GATA3-AS1as a Long Noncoding RNA Associated with Resistance to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients

Autor: Contreras-Espinosa, Laura, Alcaraz, Nicolás, De La Rosa-Velázquez, Inti A., Díaz-Chávez, José, Cabrera-Galeana, Paula, Vega, Rosa R., Reynoso-Noveron, Nancy, Maldonado-Martínez, Héctor A., González-Barrios, Rodrigo, Montiel-Manríquez, Rogelio, Bautista-Sánchez, Diana, Castro-Hernández, Clementina, Álvarez-Gómez, Rosa M., Jiménez-Trejo, Francisco, Tapia-Rodríguez, Miguel, García-Gordillo, José, Pérez-Rosas, Augusto, Bargallo-Rocha, Enrique, Arriaga-Canon, Cristian, Herrera, Luis A.
Zdroj: The Journal of Molecular Diagnostics; 20210101, Issue: Preprints
Abstrakt: 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. The GATA3-AS1transcript was overexpressed in the nonresponder group and was the most stable feature when performing selection in multiple random forest models. GATA3-AS1was experimentally validated by RT-qPCR in an extended group of 68 patients. Expression analysis confirmed that GATA3-AS1is overexpressed primarily in patients who were nonresponsive to neoadjuvant chemotherapy, with a sensitivity of 92.9%, a specificity of 75.0%, and an area under the curve of approximately 0.90, as measured by receiver operating characteristic curve analysis. 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-AS1was established as an independent predictor of response. Thus, lncRNA GATA3-AS1is proposed as a potential predictive biomarker of nonresponse to neoadjuvant chemotherapy.
Databáze: Supplemental Index