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

乳腺癌 化疗 转录组 肿瘤科 长非编码RNA 新辅助治疗 生物标志物 关贸总协定3 癌症 生物 内科学 医学 癌症研究 生物信息学 基因表达 核糖核酸 基因 转录因子 遗传学
作者
Laura Contreras-Espinosa,Nicolás Alcaraz,Inti A. De La Rosa-Velázquez,José Díaz‐Chávez,Paula Cabrera-Galeana,Rosa Rebollar‐Vega,Nancy Reynoso‐Noverón,Héctor Aquiles Maldonado-Martínez,Rodrigo González‐Barrios,Rogelio Montiel-Manríquez,Diana Bautista-Sánchez,Clementina Castro-Hernández,Rosa María Álvarez-Gómez,Francisco Jiménez-Trejo,Miguel Tapia‐Rodríguez,José Antonio García-Gordillo,Augusto Pérez-Rosas,Enrique Bargalló‐Rocha,Cristian Arriaga-Canon,Luis A. Herrera
出处
期刊:The Journal of Molecular Diagnostics [Elsevier]
卷期号:23 (10): 1306-1323 被引量:13
标识
DOI:10.1016/j.jmoldx.2021.07.014
摘要

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.
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