Aspartate β-Hydroxylase Serves As a Prognostic Biomarker for Neoadjuvant Chemotherapy in Gastric Cancer

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Mar 29

PMID 36982561

Authors

Xuejun Gan

Shen Li

Yiding Wang

Hong Du

Ying Hu

Xiaofang Xing

Xiaojing Cheng

Yan Yan

Ziyu Li

Affiliations

Soon will be listed here.

Abstract

Neoadjuvant chemotherapy (NACT) has been established as being an effective treatment for advanced gastric cancer (GC), while the predictive biomarker of NACT efficacy remains under investigation. Aspartate β-hydroxylase (ASPH) represents an attractive target which is a highly conserved transmembrane enzyme overexpressed in GC, and participates in the malignant transformation by promoting tumor cell motility. Here, we evaluated the expression of ASPH by immunohistochemistry in 350 GC tissues (including samples for NACT) and found that ASPH expression was higher in patients undergoing NACT compared with patients without NACT pre-operation. The OS and PFS time of ASPH-intensely positive patients was significantly shorter than that of the negative patients in the NACT group, while the difference was not significant in patients without NACT. We showed that ASPH knockout enhanced the inhibitory effects of chemotherapeutic drugs on the cell proliferation, migration, and invasion in vitro and suppressed tumor progression in vivo. Co-immunoprecipitation revealed that ASPH might interact with LAPTM4B to perform chemotherapeutic drug resistance. Our results suggested that ASPH might serve as a candidate biomarker to predict prognosis and a novel therapeutic target for gastric cancer patients treated with neoadjuvant chemotherapy.

Citing Articles

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