Abstract
BACKGROUND: Adenocarcinoma of the esophagogastric junction (AEG) is a common upper gastrointestinal malignancy. AIM: This study investigates the impact of long non-coding RNA NORAD on the short-term efficacy of oxaliplatin-based neoadjuvant chemotherapy in AEG. METHODS: Patients with advanced AEG received oxaliplatin-based neoadjuvant chemotherapy. Oxaliplatin- sensitive (PDCs) and oxaliplatin-resistant (PDC-Rs) primary tumor cell lines were established, and NORAD- knockdown PDC-R cells (shNORAD PDC-R) were generated. NORAD expression in pretreatment tumor tissues was measured by qRT-PCR. The half-maximal inhibitory concentration (IC50) was determined for all cell lines. RESULTS: NORAD expression correlated with Lauren classification. The low-expression group showed higher overall response rate, tumor regression grade, and pathological remission rate after chemotherapy. Pretreatment NORAD expression was an independent predictor of 3-year disease-free survival (DFS). IC50 values for PDC, PDC-R, and shNORAD PDC-R cells were 2.32, 21.41, and 3.82 μg/mL oxaliplatin, respectively. CONCLUSIONS: High pretreatment NORAD expression is an independent risk factor for poor response to neoadjuvant chemotherapy. Downregulating NORAD restores oxaliplatin sensitivity in resistant cells.