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

The Influence of Race/Ethnicity on the Transcriptomic Landscape of Uterine Fibroids.
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DOI:
10.3390/ijms241713441
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发表时间:
2023-08-30
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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--
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本研究的目的是确定选择基因的异常表达是否可以形成子宫肌瘤特征种族差异的基础。将下一代RNA测序结果分析为倍数变化[平滑肌瘤/配对子宫肌层,也称为差异表达(DF)],比较来自白色(n = 7)和黑人(n = 12)患者的标本。分析表明,95个基因在来自白色(DF α 1)的肿瘤中变化最小,但在黑人患者中显著改变超过1.5倍(增加或减少)。通过qRT-PCR在69对肌瘤中选择21个新基因进行确认。在这21个基因中,FRAT 2、SOX 4、TNFRSF 19、ACP 7、GRIP 1、IRS 4、PLEKHG 4 B、PCR、COL 24 A1、KRT 17、MMP 17、SLN、CCDC 177、FUT 2、MYO 5 B、MYOG、ZNF 703、CDC 25 A和CDCA 7差异表达的转录本编码显著较高,而与来自白色患者的肿瘤相比,来自黑人或西班牙裔患者的肿瘤中DAB 2和CAV 2的表达显著较低。Western印迹分析显示,与来自白色患者的肿瘤相比,来自黑人的肿瘤中PGR-A和总孕酮(PGR-A和PGR-B)的差异表达更大。总的来说,我们确定了一组以种族/民族依赖方式独特表达的基因,这可能形成肌瘤及其相关症状种族差异的潜在机制。
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 FRAT2, SOX4, TNFRSF19, ACP7, GRIP1, IRS4, PLEKHG4B, PGR, COL24A1, KRT17, MMP17, SLN, CCDC177, FUT2, MYO5B, MYOG, ZNF703, CDC25A, and CDCA7 was significantly higher, while the expression of DAB2 and CAV2 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.
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