Clinical and genetic determinants of vitamin D receptor expression in cutaneous melanoma patients.

IF 1.5 4区 医学 Q3 DERMATOLOGY
Melanoma Research Pub Date : 2024-04-01 Epub Date: 2024-02-13 DOI:10.1097/CMR.0000000000000929
Julie De Smedt, Claudia Aura, Sofie Van Kelst, Laudine Janssen, Vivien Marasigan, Veerle Boecxstaens, Marguerite Stas, Kris Bogaerts, Ann Belmans, Isabelle Cleynen, Dirk Vanderschueren, Katleen Vandenberghe, Oliver Bechter, Arjen Nikkels, Tinne Strobbe, Gabriella Emri, Dieter Lambrechts, Marjan Garmyn
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Abstract

Decrease of vitamin D receptor (VDR) expression is observed in melanocytic naevi and melanoma compared to normal skin. Little is known about factors influencing VDR expression in cutaneous melanoma (CM). We investigated the correlation of VDR expression in CM with 25-hydroxy vitamin D (25OHD) levels, demographic/clinical parameters, genetic variants of VDR and pathology of the primary tumor. Demographic/clinical parameters were recorded in 407 prospectively recruited CM patients of a multi-center controlled study (ViDMe trial). We determined VDR expression both in the nucleus and in the cytoplasm by semi-quantitative assessment in CM tissue using histochemistry in 279 patients, expressed in percentages and histoscore (H-score). Genomic DNA from 332 patients was extracted to genotype thirteen VDR single nucleotide polymorphisms (SNPs) using TaqMan. VDR expression in CM tissue from 279 patients was correlated with clinical/demographic parameters and 25OHD levels (univariable and multivariable analysis), VDR SNPs (univariable analysis) and pathology parameters of primary CM tissue (univariable analysis). Cytoplasmic VDR expression was increased in patients who stated to have a high sun exposure during their life compared to patients with low sun exposure (p H-score,univariable : 0.001, p H-score,multivariable : 0.004). The A allele of the genetic VDR polymorphism Fok1 was associated with a higher expression of the VDR in the cytoplasm (p cytoplasmic, univariable : 0.001 and p H-score, univariable : 0.02). In the primary tumor, presence of mitosis (p nucleus,%, univariable : 0.002) and perineural invasion (p nucleus,%,univariable : 0.03) were significantly associated with low nuclear VDR expression. ClinicalTrials.gov Identifier: NCT01748448.

皮肤黑色素瘤患者维生素 D 受体表达的临床和遗传决定因素。
与正常皮肤相比,在黑素细胞痣和黑色素瘤中观察到维生素 D 受体(VDR)表达减少。人们对影响皮肤黑色素瘤(CM)中 VDR 表达的因素知之甚少。我们研究了VDR在CM中的表达与25-羟基维生素D(25OHD)水平、人口学/临床参数、VDR基因变异和原发肿瘤病理的相关性。在一项多中心对照研究(ViDMe 试验)中,我们记录了 407 名前瞻性招募的 CM 患者的人口统计学/临床参数。我们使用组织化学方法对 279 名患者的 CM 组织进行了半定量评估,确定了 VDR 在细胞核和细胞质中的表达,以百分比和组织评分(H-score)表示。提取 332 名患者的基因组 DNA,使用 TaqMan 对 13 个 VDR 单核苷酸多态性 (SNP) 进行基因分型。279 名患者的 CM 组织中 VDR 的表达与临床/人口学参数和 25OHD 水平(单变量和多变量分析)、VDR SNPs(单变量分析)和原发性 CM 组织的病理学参数(单变量分析)相关。与日晒较少的患者相比,日晒较多的患者细胞质 VDR 表达增加(pH 值分数,单变量:0.001;pH 值分数,多变量:0.004)。在原发性肿瘤中,有丝分裂(pnucleus,%,单变量:0.002)和神经周围侵袭(pnucleus,%,单变量:0.03)与核VDR低表达显著相关。ClinicalTrials.gov Identifier:NCT01748448。
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来源期刊
Melanoma Research
Melanoma Research 医学-皮肤病学
CiteScore
3.40
自引率
4.50%
发文量
139
审稿时长
6-12 weeks
期刊介绍: ​​​​​​Melanoma Research is a well established international forum for the dissemination of new findings relating to melanoma. The aim of the Journal is to promote the level of informational exchange between those engaged in the field. Melanoma Research aims to encourage an informed and balanced view of experimental and clinical research and extend and stimulate communication and exchange of knowledge between investigators with differing areas of expertise. This will foster the development of translational research. The reporting of new clinical results and the effect and toxicity of new therapeutic agents and immunotherapy will be given emphasis by rapid publication of Short Communications. ​Thus, Melanoma Research seeks to present a coherent and up-to-date account of all aspects of investigations pertinent to melanoma. Consequently the scope of the Journal is broad, embracing the entire range of studies from fundamental and applied research in such subject areas as genetics, molecular biology, biochemistry, cell biology, photobiology, pathology, immunology, and advances in clinical oncology influencing the prevention, diagnosis and treatment of melanoma.
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