2529:前列腺癌中特定种族CYP2R1与昼夜节律基因的相关性

Isaacson B. Adelani, S. Rotimi, C. Yates, M. Campbell
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引用次数: 0

摘要

简介:维生素D在其激素形式,1α,25-二羟基维生素D3 (1,25(OH)2D3)结合维生素D受体(VDR)来调节基因,例如,在骨骼矿化。然而,它在调节细胞凋亡、增殖和炎症方面也有其他强有力的生物学功能。在癌变过程中,125 (OH)2D3可能被用来调节这些关键途径。同样清楚的是,与欧洲裔美国人(EA)相比,非洲裔美国人(AA)患前列腺癌的男性之间存在着常见的癌症差异。AA男性的发病率较高,死亡率是EA男性的2 - 3倍。不同的研究小组认为,125 (OH)2D3水平和/或VDR功能是AA男性前列腺癌发病率增加的危险因素。顺便说一句,有报道表明VD在调节昼夜节律(CR)中起着至关重要的作用。因此,有必要了解和评估1,25(OH) 2d3依赖性CR调控及其与前列腺癌种族差异的关系。本研究旨在确定AA和EA中是否存在VD代谢酶的差异表达,并评估其差异表达是否与CR基因相关。方法:查询癌症基因组图谱研究网络(TCGA) 2015年数据库中VD代谢酶和CR基因的表达情况。我们对AA和EA在前列腺癌中的表达进行了检索,查询的VD代谢酶有CYP2R1、CYP24A1、CYP27B1、CYP27A1,查询的CR基因有ARNTL、CLOCK、CRY1、CRY2、CSNK1E、NPAS2、PER1、PER2、PER3和TIMELESS。评估前列腺腺癌AA和EA的种族差异表达,并采用Pearson相关法进行相关性研究。结果:与EA相比,AA中VD代谢酶、CYP2R1、CR基因、ARNTL显著上调。虽然在两个种族中,cyp1与CLOCK、CRY2和PER3呈负相关,但在EA中,cyp1与CR基因CRY1呈正相关,在AA中与CR基因NPAS2和CSNK1E呈负相关。然而,在EA和AA中,CYP2R1和ARNTL之间没有明显的相关性。结论:种族影响与前列腺癌的关系与VD代谢和CR调节有关。因此,阐明CYP2R1在前列腺癌中与VD水平和CR调节相关的调控是至关重要的,特别是关注种族差异。引用格式:Isaacson Bababode Adelani, Solomon Oladapo Rotimi, Clayton Yates, Moray Campbell。前列腺癌中特定种族CYP2R1与昼夜节律基因的相关性[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):2529。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Abstract 2529: Specific racial CYP2R1 correlation with circadian rhythm genes in prostate adenocarcinoma
Introduction: Vitamin D in its hormonal form, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) binds to the vitamin D receptor (VDR) to regulate genes, for example, in skeletal mineralization. However, it also has other potent biological functions in regulating apoptosis, proliferation, and inflammation. In carcinogenesis, 1,25(OH)2D3 may be exploited to regulate these crucial pathways. It is also clear that a frequent cancer disparity exists amongst African American (AA) men with prostate cancer compared to European Americans (EA). AA men show a higher incidence rate and two to three times increased risk of mortality than EA counterparts. Various groups have suggested that 1,25(OH)2D3 levels and/or VDR functions are risk factors linked with increased prostate cancer incidence in AA men. Incidentally, reports showed that VD plays a crucial role in regulating circadian rhythm (CR). There is, therefore, a need to understand and evaluate 1,25(OH)2D3-dependent CR regulation and the association with racial disparity in prostate cancer. This study aimed to determine if there are differentially expressed VD metabolic enzymes in AA and EA and evaluate if the differential expression correlates with CR genes. Methods: The Cancer Genome Atlas Research Network (TCGA), 2015 database was queried for expression of VD metabolizing enzymes and CR genes. The search was carried out on prostate adenocarcinoma expressions of AA and EA. VD metabolizing enzymes queried are CYP2R1, CYP24A1, CYP27B1, CYP27A1, while CR genes queried include ARNTL, CLOCK, CRY1, CRY2, CSNK1E, NPAS2, PER1, PER2, PER3, and TIMELESS. Prostate adenocarcinoma racial differential expressions of AA and EA were evaluated, and a correlation study was done using the Pearson correlation. Results: VD metabolic enzyme, CYP2R1, and CR gene, ARNTL were significantly upregulated in AA compared to EA counterparts. Although CYPR1 correlates negatively with CLOCK, CRY2, and PER3 in both races, CYPR1 specifically showed a positive correlation with CR gene CRY1 in EA and negative correlations with CR genes NPAS2 and CSNK1E in AA. However, a significant correlation between CYP2R1 and ARNTL in EA and AA was not observed. Conclusion: The data suggest a relationship between racial influence and prostate cancer associated with VD metabolism and CR regulation. Hence, it is crucial to elucidate CYP2R1 regulation in prostate cancer related to VD levels and CR regulation, especially with a focus on racial disparities. Citation Format: Isaacson Bababode Adelani, Solomon Oladapo Rotimi, Clayton Yates, Moray Campbell. Specific racial CYP2R1 correlation with circadian rhythm genes in prostate adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2529.
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