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种族/民族对子宫肌瘤转录组景观的影响。

The Influence of Race/Ethnicity on the Transcriptomic Landscape of Uterine Fibroids.

机构信息

Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.

The Lundquist Institute for Biomedical Innovation, Torrance, CA 90502, USA.

出版信息

Int J Mol Sci. 2023 Aug 30;24(17):13441. doi: 10.3390/ijms241713441.

Abstract

The objective of this study was to determine if the aberrant expression of select genes could form the basis for the racial disparity in fibroid characteristics. The next-generation RNA sequencing results were analyzed as fold change [leiomyomas/paired myometrium, also known as differential expression (DF)], comparing specimens from White (n = 7) and Black (n = 12) patients. The analysis indicated that 95 genes were minimally changed in tumors from White (DF ≈ 1) but were significantly altered by more than 1.5-fold (up or down) in Black patients. Twenty-one novel genes were selected for confirmation in 69 paired fibroids by qRT-PCR. Among these 21, coding of transcripts for the differential expression of , , , , , , , , , , , , , , , , , , and was significantly higher, while the expression of and was significantly lower in tumors from Black or Hispanic patients compared with tumors from White patients. Western blot analysis revealed a greater differential expression of PGR-A and total progesterone (PGR-A and PGR-B) in tumors from Black compared with tumors from White patients. Collectively, we identified a set of genes uniquely expressed in a race/ethnicity-dependent manner, which could form the underlying mechanisms for the racial disparity in fibroids and their associated symptoms.

摘要

本研究旨在确定特定基因的异常表达是否可以作为肌瘤特征种族差异的基础。对来自白人(n=7)和黑人(n=12)患者的标本进行下一代 RNA 测序结果分析,以倍数变化(肌瘤/配对的子宫肌层,也称为差异表达(DF))进行分析。分析表明,95 个基因在白人肿瘤中变化极小(DF≈1),但在黑人患者中则发生了超过 1.5 倍(上调或下调)的显著改变。通过 qRT-PCR 在 69 对纤维瘤中选择了 21 个新基因进行确认。在这 21 个基因中,编码 、 、 、 、 、 、 、 、 、 、 、 、 、 和 的转录本差异表达显著升高,而黑人或西班牙裔患者肿瘤中的 和 的表达显著低于白人患者肿瘤。Western blot 分析显示,与白人患者的肿瘤相比,黑人患者的肿瘤中 PGR-A 和总孕激素(PGR-A 和 PGR-B)的差异表达更大。综上所述,我们鉴定了一组以种族/民族依赖方式特异性表达的基因,这些基因可能构成了肌瘤及其相关症状种族差异的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a4/10487975/43aff7aa84e3/ijms-24-13441-g001.jpg

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