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Transcriptome Analysis Identifies GATA3-AS1 as a Long Noncoding RNA Associated with Resistance to Neoadjuvant
Laura Contreras-Espinosa1, Nicolás Alcaraz2, Inti A De La Rosa-Velázquez3
1Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, National Autonomous University of Mexico (UNAM), Tlalpan, Mexico City, México.
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.
Insights
Long noncoding RNAs (lncRNAs) like GATA3-AS1 may predict breast cancer response to neoadjuvant chemotherapy. Overexpression of GATA3-AS1 indicates nonresponse, offering a potential biomarker for treatment selection.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Breast cancer is a leading cause of mortality in women globally.
- Neoadjuvant chemotherapy is a key treatment for locally advanced breast cancer.
- Predictive biomarkers for chemotherapy response are crucial for personalized treatment.
Purpose of the Study:
- To investigate the role of long noncoding RNAs (lncRNAs) as biomarkers for predicting neoadjuvant chemotherapy response in breast cancer.
- To identify specific lncRNAs associated with treatment response or nonresponse.
Main Methods:
- RNA sequencing was used to profile lncRNA expression in breast cancer patient biopsies.
- Patients were categorized into responders and nonresponders to neoadjuvant chemotherapy.
- Quantitative RT-PCR validated the expression of candidate lncRNAs in an extended patient cohort.
Main Results:
- The lncRNA GATA3-AS1 was found to be significantly overexpressed in patients who did not respond to neoadjuvant chemotherapy.
- GATA3-AS1 demonstrated high sensitivity (92.9%) and specificity (75.0%) in predicting nonresponse.
- Statistical modeling identified GATA3-AS1 as an independent predictor of treatment response, particularly in luminal B-like breast cancer.
Conclusions:
- The lncRNA GATA3-AS1 is a potential predictive biomarker for nonresponse to neoadjuvant chemotherapy in breast cancer patients.
- This finding could aid in tailoring treatment strategies and improving patient outcomes.
- Further research is warranted to validate GATA3-AS1 in broader clinical settings.
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