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

Ruinuo Jia, Youjia Mi, Xiang Yuan, Dejiu Kong, Wanying Li, Ruonan Li, Bingbing Wang, Yafei Zhu, Jinyu Kong, Zhikun Ma, Na Li, Qiangjian Mi, Shegan Gao, Ruinuo Jia, Youjia Mi, Xiang Yuan, Dejiu Kong, Wanying Li, Ruonan Li, Bingbing Wang, Yafei Zhu, Jinyu Kong, Zhikun Ma, Na Li, Qiangjian Mi, Shegan Gao

Abstract

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.

Conflict of interest statement

The authors declare no conflicts of interest.

Copyright © 2020 Ruinuo Jia et al.

Figures

Figure 1
Figure 1
Study flow chart.
Figure 2
Figure 2
The correlation between GASC1 level and clinical parameters in ESCC patients. GASC1 expression in all ESCC tissues was measured by immunohistochemistry. (a) The expression of GASC1 in different grade tumor tissues from ESCC patients was detected. One representative micrograph is shown. Scale bar represents 20 μm. (b) The expression of GASC1 in different grade tissues (G1, G2 + G3) from ESCC patients is presented as a scatter diagram. (c) GASC1 expression in ESCC tissues with positive and negative lymph node metastasis is shown as a scatter diagram. (d) GASC1 expression in different tumor tissues based upon T score (T1 + T2, T3 + T4) is shown as a scatter diagram. (e) GASC1 expression in ESCC tissues with different clinical parameters analyzed by immunohistochemistry is shown as a histogram with a staining score.
Figure 3
Figure 3
Kaplan-Meier survival curves for ESCC patients with lower and higher GASC1 expressions.

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Source: PubMed

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