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Neoadjuvant chemotherapy (NCT) is a standard care for esophageal squamous cell carcinoma (ESCC), but the efficacy is unsatisfactory. Cancer stem cells (CSCs) play key roles in chemotherapy resistance. Gene amplified in squamous cell carcinoma 1 (GASC1) is a neoteric gene in stemness maintaining of ESCC. We aimed to reveal whether GASC1 could be a predictive biomarker for NCT in ESCC. ESCC patients (T2-4N0-2M0) were evaluated for GASC1 expression using immunohistochemical staining and classified as GASC1-low group (GLG) and GASC1-high group (GHG). NCT was delivered in two cycles and then the surgery was completed. Primary endpoints were tumor regression grade (TRG) and objective response rate (ORR); secondary endpoints were radical surgical resection (R0) rate and three-year overall survival (OS). 60 patients were eligible with evaluable outcomes: 24 in GHG and 36 in GLG. Between GHG and GLG, TRG1, TRG2, TRG3, and TRG4 were 0 : 16.7%, 20.8% : 41.7%, 58.3% : 36.1%, and 20.8% : 5.6%, respectively (P=0.006); ORR and R0 rate were 33.3% : 69.4% (P=0.006) and 75% : 94.4% (P=0.046), respectively; the median OS was 20 : 32 (months) (P=0.0356). No significant difference in the three-year OS was observed between GHG and GLG: 29.2% : 41.7% (P=0.24). Furthermore, the GASC1 expression level was associated with poor OS independent of other factors by univariate and multivariate analyses. Therefore, GASC1 might be a potential biomarker to predict NCT efficacy for ESCC.

GASC1-Adapted Neoadjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma: A Prospective Clinical Biomarker Trial