江苏大学学报（医学版）2024，Vol.34Issue(1)：19-24,6.DOI:10.13312/j.issn.1671-7783.y230206
ONECUT2高表达介导胃癌复发患者5-FU化疗耐药
High expression of ONECUT2 mediates 5-FU chemotherapy resistance in patients with recurrent gastric cancer
摘要
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.关键词
One cut结构域家族成员2/胃癌复发/5-FU耐药/GSEA/细胞毒性/半数抑制浓度Key words
ONECUT2/gastric cancer relapse/5-FU resistance/GSEA/cytotoxicity/IC50分类
医药卫生引用本文复制引用
朱海峰,陈述,龙卫国,王旭..ONECUT2高表达介导胃癌复发患者5-FU化疗耐药[J].江苏大学学报（医学版）,2024,34(1):19-24,6.基金项目
江苏省自然科学基金面上项目(BK20211124) （BK20211124）
