FANCD2在子宫内膜癌中的表达及其意义

Expression and significance of FANCD2 in endometrial carcinoma

目的:分析范可尼贫血相关基因D2(FANCD2)在子宫内膜癌(UCEC)的表达及其意义。方法:生物信息学分析FANCD2在UCEC中的表达、预后及与免疫细胞浸润的关系;逆转录聚合酶链式反应(RT-qPCR)检测FANCD2在62例子宫内膜癌和28例正常子宫内膜组织中的表达,分析其表达与临床病理特征的关系;敲减(KD)技术构建低表达的FANCD2载体,与空白载体一同转染Ishikawa细胞,检测不同浓度顺铂处理后Ishikawa细胞、Ishikawa-Vector、Ishikawa-FANCD2KD内谷胱甘肽(GSH)和脂质氧化(MDA)水平。结果:生物信息学分析显示,FANCD2在UCEC组织中高表达(P<0.05),且高表达的患者有较差的预后(P<0.05);免疫浸润分析显示,常见免疫细胞(B细胞、CD8^(+)T细胞、巨噬细胞、中性粒细胞和树突状细胞)的浸润与FANCD2负相关(P<0.05);与Ishikawa-Vector相比,经不同浓度顺铂处理后的Ishikawa-FANCD2KD中GSH水平降低(P<0.05);MDA水平增高(P<0.05)。结论:FANCD2在UCEC中高表达,FANCD2下调可能通过铁死亡增加Ishikawa细胞对顺铂的敏感性。

Objective:To analyze the expression and significance of Fanconi anemia complementation group D2(FANCD2)in uterine corpus endometrial carcinoma(UCEC).Methods:The expression,prognosis and relationship between FANCD2 and immune cell infiltration in UCEC were analyzed by bioinformatics.The expression of FANCD2 in 62 cases of endometrial carcinoma and 28 cases of normal endometrial tissue were detected by RT-qPCR,and the relationship between the expression of FANCD2 and clinicopathologic features was analyzed.The FANCD2 knockdown plasmid was constructed and transfected into Ishikawa cells to detect the levels of GSH and MDA by different concentrations of cisplatin.Results:Bioinformatics analysis showed that FANCD2 was highly expressed in UCEC tissues(P<0.05),and patients with high expression had poor prognosis(P<0.05).Immunoinfiltration analysis showed that immun cells(B cell,CD8^(+)T cell,macrophage,neutrophil,dendritic cell)infiltration was negatively correlated with FANCD2 expression(P<0.05).Compared with Ishikawa-Vector,the levels of GSH in Ishikawa-FANCD2KD treated with different concentrations of cisplatin were decreased(P<0.05),while the levels of MDA were increased(P<0.05).Conclusion:FANCD2 is highly expressed in UCEC,and down-regulation of FANCD2 may increase the cisplatin sensitivity of Ishikawa cells through ferroptosis.