ONECUT2高表达介导胃癌复发患者5-FU化疗耐药

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Abstract Objective： To explore whether one cut domain family member 2 (ONECUT2) transcription factor could be a therapeutic target for 5-FU resistant gastric cancer (GC) relapsed patients. Methods: The Cancer Genome Atlas (TCGA) database was used to analyze the expression level of ONECUT2 in GC patients and GC relapsed patients. Gene set enrichment analyses (GSEA) were performed using STAD patients from TCGA to explore the correlation between ONECUT2 and biological processes related to drug metabolism. CCK-8 cytotoxic assays were performed to evaluate the role of ONECUT2 knockdown or overexpression on 5-FU resistance in gastric cancer cell lines. 30 relapsed GC patients with previously resected tumor samples were recruited to analyze the correlation between ONECUT2 expression level and 5-FU treatment efficacy. Results: According to the results of TCGA data analysis, in GC patients with chemotherapeutic treatment and cancer reoccurrence events, higher ONECUT2 level contributed to shorter disease-free interval. GSEA results suggested that upregulated ONECUT2 was positively correlated with xenobiotic drug metabolism, and which was related to drug resistance in GC patients. ONECUT2 knockdown reduced IC50 value of 5-FU in GC cells in vitro; on the contrast, ONECUT2 overexpression increased IC50 value of 5-FU in GC cells in vitro. The sensitivity of 5-FU treatment was negatively correlated with ONECUT2 mRNA level of tumor samples derived from 30 GC patients who relapsed after surgical resection. Conclusion: Relapsed GC patients had a higher expression of ONECUT2, and higher ONECUT2 expression level was positively related to 5-FU resistance in relapsed GC patients. These results provided a potential therapeutic target for GC treatment.

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Received: 03 September 2023

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	Articles by authors
	ZHU Haifeng1
	CHEN Shu2
	LONG Weiguo3
	WANG Xu4

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ZHU Haifeng1,CHEN Shu2,LONG Weiguo3等. High expression of ONECUT2 mediates 5-FU chemotherapy resistance in patients with recurrent gastric cancer[J]. Journal of Jiangsu University(Medicine Edition), 2024, 24(01): 19-24.

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http://zzs.ujs.edu.cn/xbyxb/EN/ OR http://zzs.ujs.edu.cn/xbyxb/EN/Y2024/V24/I01/19

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