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FANCD2在子宫内膜癌中的表达分析

Expression Analysis of FANCD2 in Endometrial Carcinoma.

作者信息

Zhang Li, Chang Juan, Wu Xiuwei

机构信息

Department of Obstetrics and Gynecology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People's Republic of China.

Department of Hematology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People's Republic of China.

出版信息

Cancer Manag Res. 2024 Dec 5;16:1715-1725. doi: 10.2147/CMAR.S488275. eCollection 2024.

DOI:10.2147/CMAR.S488275
PMID:39654637
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11626963/
Abstract

BACKGROUND

Cisplatin is a major chemotherapy drug in the treatment of Uterine Corpus Endometrial carcinoma (UCEC), and drug resistance often limits its efficacy. Studying the mechanism of cisplatin resistance in endometrial carcinoma is of great clinical importance. This study aims to analyze the expression and value of FANCD2 in UCEC.

METHODS

The expression of FANCD2, prognosis, and relationship between FANCD2 and immune cell infiltration in UCEC were analyzed by using bioinformatics. The expression levels of FANCD2 in 62 cases of endometrial carcinoma and 28 cases of normal endometrial tissues were detected by RT-PCR, and the relationship between FANCD2 expression and clinicopathological features was analyzed. A FANCD2 knockdown plasmid was constructed and transfected into Ishikawa cells to detect the levels of GSH and MDA in the presence of different concentrations of cisplatin.

RESULTS

Bioinformatics analysis showed that FANCD2 was highly expressed in UCEC tissues, and patients with high expression had poor prognosis. Immune infiltration analysis revealed that (B cell, CD8 T cell, macrophage, neutrophil, dendritic cell) infiltration was negatively correlated with FANCD2 expression. Compared with those in Ishikawa-Vector, the levels of GSH significantly decreased and those of MDA significantly increased in Ishikawa-FANCD2KD treated with different concentrations of cisplatin.

CONCLUSION

FANCD2 was highly expressed in UCEC, and the down-regulation of FANCD2 affected the levels of GSH and MDA to increase the cisplatin sensitivity of Ishikawa cells.

摘要

背景

顺铂是治疗子宫内膜癌的主要化疗药物，而耐药性常常限制其疗效。研究子宫内膜癌顺铂耐药机制具有重要的临床意义。本研究旨在分析FANCD2在子宫内膜癌中的表达及价值。

方法

运用生物信息学分析FANCD2在子宫内膜癌中的表达、预后以及FANCD2与免疫细胞浸润的关系。采用RT-PCR检测62例子宫内膜癌组织和28例正常子宫内膜组织中FANCD2的表达水平，并分析FANCD2表达与临床病理特征的关系。构建FANCD2敲低质粒并转染至Ishikawa细胞，检测不同浓度顺铂作用下细胞内谷胱甘肽（GSH）和丙二醛（MDA）水平。

结果

生物信息学分析显示，FANCD2在子宫内膜癌组织中高表达，高表达患者预后较差。免疫浸润分析表明，（B细胞、CD8 + T细胞、巨噬细胞、中性粒细胞、树突状细胞）浸润与FANCD2表达呈负相关。与Ishikawa-Vector组相比，不同浓度顺铂处理的Ishikawa-FANCD2KD组中GSH水平显著降低，MDA水平显著升高。

结论

FANCD2在子宫内膜癌中高表达，下调FANCD2影响GSH和MDA水平，从而增加Ishikawa细胞对顺铂的敏感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45f/11626963/5c0157e2fa99/CMAR-16-1715-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45f/11626963/259b4c5b62a3/CMAR-16-1715-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45f/11626963/7e5b9fc6dcdc/CMAR-16-1715-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45f/11626963/9a493e490576/CMAR-16-1715-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45f/11626963/231d5b1a09ef/CMAR-16-1715-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45f/11626963/6ef8bfb420ec/CMAR-16-1715-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45f/11626963/5c0157e2fa99/CMAR-16-1715-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45f/11626963/259b4c5b62a3/CMAR-16-1715-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45f/11626963/7e5b9fc6dcdc/CMAR-16-1715-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45f/11626963/9a493e490576/CMAR-16-1715-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45f/11626963/231d5b1a09ef/CMAR-16-1715-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45f/11626963/6ef8bfb420ec/CMAR-16-1715-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45f/11626963/5c0157e2fa99/CMAR-16-1715-g0006.jpg

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本文引用的文献

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Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.2022 年全球癌症统计数据：全球 185 个国家和地区 36 种癌症的发病率和死亡率全球估计数。
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铁死亡：机制及其在糖尿病及其并发症中的作用
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Ferroptosis-Related Gene SLC1A5 Is a Novel Prognostic Biomarker and Correlates with Immune Microenvironment in HBV-Related HCC.铁死亡相关基因SLC1A5是一种新型的预后生物标志物，与乙型肝炎病毒相关肝癌的免疫微环境相关。
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FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma.FANCD2 通过调控骨肉瘤中的 JAK2/STAT3 通路抑制铁死亡。
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