疣状表皮痣(VEN)是在出生时或在儿童早期出现的角质化表皮痣。它们表现出一系列的表现,取决于病人的年龄。VEN在临床实践中很少遇到,VEN的系统性和综合性临床特征尚未得到很好的研究。此外,基于串联质量标签(TMT)的定量蛋白质组学与VEN表型之间的关联尚不清楚.
本研究调查了炎性线性VEN(ILVEN)和局部VEN之间的临床特征和病变蛋白质组学差异。
这项回顾性研究纳入了125例组织病理学诊断为VEN的患者,他们在2019年至2021年期间到我们医院就诊。我们使用自行设计的问卷收集所有VEN患者的临床数据。使用TMT蛋白质组学技术分析VEN病变中蛋白质的表达。
总共,对125例VEN患者进行了评估,包括67例(53.60%)局部VEN患者和58例(46.40%)ILVEN患者。在性别上没有发现显著差异,发病年龄,局部VEN和ILVEN患者的病变位置(均P>0.05)。ILVEN患者与局部VEN患者的发病部位和瘙痒评分差异均有统计学意义(均P<0.05)。根据TMT蛋白质组学研究结果,在ILVEN病变中,相对于VEN病变,89种蛋白质上调或下调至少1.3倍(上调:38,下调:51;P<0.05)。ILVEN和局部VEN病变前10位差异表达蛋白为OGN,NT5C3A,ADD1,OLFML1,DHRS1,CALML5,SAMHD1,SFRP2,SPRR1B,SERPINB13上调的蛋白主要参与中性粒细胞的活化,中性粒细胞介导的免疫,和p53信号通路(hsa04115)。下调蛋白主要参与细胞对细胞因子刺激的反应,细胞粘附,Th1和Th2细胞分化。总的来说,基于ILVEN和局部VEN之间的差异表达蛋白,可能与炎症发病机制相关的五种途径,包括CAM(P=0.006),Th1和Th2细胞分化(P=0.017),PPAR信号通路(P=0.023),Th17细胞分化(P=0.024),p53信号通路(P=0.041)。
患者的临床数据显示ILVEN病变表现为剧烈瘙痒和炎性改变。ILVEN与局部VEN的差异表达蛋白主要参与与瘙痒发病机制相关的多种炎症相关通路。
临床特征和蛋白质组学研究中的小样本量是我们研究中最重要的限制之一。ILVEN瘙痒发病机制中的炎症相关蛋白和信号通路尚未探讨。
在这项研究中,我们发现ILVEN患者的病变表现为剧烈瘙痒和炎症改变.在ILVEN病变中,相对于VEN病变,总共89种蛋白质上调或下调至少1.3倍(上调:38,下调:51;P<0.05)。另一方面,ILVEN瘙痒的病因主要与炎症有关,但确切的机制仍不清楚。我们发现ILVEN和局部VEN之间的差异表达蛋白富集了5条可能与炎症和瘙痒的发病机制有关的途径。
Verrucous epidermal nevus (VEN) are keratinocytic epidermal nevus that appear at birth or in early childhood. They exhibit a range of manifestations, depending on the patient\'s age. VEN are rarely encountered in clinical practice, and the systemic and comprehensive clinical characteristics of VEN have not been well investigated. Furthermore, the association between tandem mass tag (TMT)-based quantitative proteomics and the VEN phenotype is still unclear.
This study investigated the differences in the clinical characteristics and lesion proteomics between inflammatory linear VEN (ILVEN) and local VEN.
This retrospective study enrolled 125 patients with histopathologically diagnosed VEN who presented to our hospital between 2019 and 2021. We collected the clinical data of all patients with VEN using a self-designed questionnaire. The expression of proteins in VEN lesions was analyzed using TMT proteomics technology.
In total, there were 125 patients with VEN that were evaluated, including 67 (53.60%) patients with local VEN and 58 (46.40%) with ILVEN. No significant differences were found in sex, onset age, and lesion location between patients with local VEN and those with ILVEN (all P > 0.05). Significant differences were found in the onset site and pruritus scores between patients with ILVEN and those with local VEN (all P < 0.05). According to the TMT proteomics results, 89 proteins were up or downregulated with at least 1.3-fold (upregulated: 38, downregulated: 51; P < 0.05) in ILVEN lesions relative to VEN lesions. The top 10 differentially expressed proteins between ILVEN and local VEN lesions were OGN, NT5C3A, ADD1, OLFML1, DHRS1, CALML5, SAMHD1, SFRP2, SPRR1B, and SERPINB13. The upregulated proteins are mainly involved in neutrophil activation, neutrophil-mediated immunity, and p53 signaling pathway (hsa04115). The downregulated proteins are mainly involved in cellular response to cytokine stimulus, cell adhesion, Th1 and Th2 cell differentiation. In total, based on the differentially expressed proteins between ILVEN and local VEN, five pathways that may be associated with the pathogenesis of inflammation, including CAMs (P = 0.006), Th1 and Th2 cell differentiation (P = 0.017), PPAR signaling pathway (P = 0.023), Th17 cell differentiation (P = 0.024), and p53 signaling pathway (P = 0.041).
Clinical data of the patients revealed that ILVEN lesions presented with intense pruritus and inflammatory change. Differentially expressed proteins between ILVEN and local VEN are mainly involved in multiple inflammation related pathways associated with the pathogenesis mechanisms of pruritus.
The small sample size in clinical characteristic and proteomics study is one of the most significant limitations in our study. The inflammation associated proteins and signal pathways in the pathogenesis of pruritus in ILVEN is not explored.
In this study, we found the lesions of ILVEN patients presented with intense pruritus and inflammational change. A total of 89 proteins were up or downregulated with at least 1.3-fold (upregulated: 38, downregulated: 51; P < 0.05) in ILVEN lesions relative to VEN lesions. On the other hand, the etiology of itch in ILVEN mainly associated with inflammation, but the exact mechanisms was still unclear. We found the differentially expressed proteins between ILVEN and local VEN enriched five pathways that may be associated with the pathogenesis of inflammation and pruritus.