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

Breast cancer is one of the leading causes ofmortality inwomenworldwide, and neoadjuvant chemotherapy has emerged as an option for themanagement of locally advanced breast cancer. Extensive efforts have beenmade 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 statisticalmodelwas based on luminal B-like patients and adjusted bymenopausal status and phenotype (odds ratio, 37.49; 95% CI, 6.74-208.42; PZ0.001); 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.

Automated summary

Breast cancer is a major cause of mortality in women globally, and neoadjuvant chemotherapy has emerged as a treatment option for locally advanced breast cancer. The lncRNA GATA3-AS1 has been proposed as a potential predictive biomarker of nonresponse to neoadjuvant chemotherapy.