AGR2 – a Novel Predictor of Neoadjuvant Chemoradiotherapy Response in Esophageal Squamous Cell Carcinoma

Abstract

BackgroundEsophageal squamous cell carcinoma (ESCC) still has a poor prognosis despite the use of multidisciplinary therapy. In the locally advanced stage, neoadjuvant chemoradiotherapy (nCRT) followed by surgery might provide survival benefits to some patients. MethodsIn this study, we aimed to identify biomarker to predict tumor response against neoadjuvant chemoradiotherapy (nCRT) by next-generation sequencing (NGS).ResultsOur data showed that 464 genes was differentially expressed ESCC specimens, in which AGR2 was 2.8 fold up-regulated in the patients with Non-complete response before nCRT than complete response group. In vitro study showed that, AGR2 was significantly reduced in AGR2 knockdown CE146T/VGH, TE2, and CE48T/VGH cells. MTT assay indicated that cell viability of AGR2-knockdown TE-2 cell line significantly decreased following 2.5µM cisplatin and 3µM 5-FU treatment. Furthermore, 6µM cisplatin and 20 µM 5-FU treatment greatly decreased AGR2-knockdown-CE48T/VGH, CE146T/VGH and TE-2 cells compared to control group. We also found in AGR2-knockdown cells, that protein level of p21 was increased in comparison with the control group. ConclusionsThis study suggest that AGR-2 as a promising and potential prediction gene marker dataset for response to neoadjuvant chemoradiation in ESCC.