Rizzello Antonio, Franck Julien, Pellegrino Marcello, De Nuccio Francesco, Simeone Pasquale, Fiore Giovanni, Di Tommaso Silvia, Malvasi Antonio, Tinelli Andrea, Fournier Isabelle, Salzet Michel, Maffia Michele, Vergara Daniele
Department of Biological and Environmental Sciences and Technologies, University of Salento, via Monteroni, Lecce, Italy.
Curr Protein Pept Sci. 2017;18(2):167-174. doi: 10.2174/1389203717666160322150603.
Uterine leiomyoma is a benign smooth muscle tumor characterized by a high incidence in women of reproductive age. The aetiology of this tumor is still unknown but established risk factors include high levels of female hormones, family history, African ancestry, early age of menarche and obesity. Here, to identify proteomic features associated with this tumor type, we performed a liquid chromatography-mass spectrometry (LC-MS/MS) analysis of uterine myomas. The identified proteins were subjected to a gene ontology analysis to generate biological functions, molecular processes, and protein networks that were relevant to the uploaded dataset. Pathway-based analysis was an effective approach to investigate the molecular mechanisms underlying the disease and to create biological hypotheses about regulation of our proteins including the identification of upstream regulators and main protein nodes. Moreover, proteomic and in silico data were combined with immunohistochemistry and western blotting to identify a group of proteins representative of some selected pathways, with a dysregulated expression in myoma, pseudocapsule, and normal myometrium samples. Based on these results, we confirmed the over-expression of extracellular matrix components, and estrogen and progesterone receptors in uterine myomas, and proposed biological networks, canonical pathways and functions that may be relevant to the pathophysiology of this tumor.
子宫肌瘤是一种良性平滑肌肿瘤，其特征是在育龄女性中发病率较高。这种肿瘤的病因尚不清楚，但已确定的风险因素包括高水平的女性激素、家族史、非洲血统、初潮年龄早和肥胖。在此，为了确定与这种肿瘤类型相关的蛋白质组学特征，我们对子宫肌瘤进行了液相色谱 - 质谱联用（LC-MS/MS）分析。对鉴定出的蛋白质进行基因本体分析，以生成与上传数据集相关的生物学功能、分子过程和蛋白质网络。基于通路的分析是研究该疾病潜在分子机制以及创建关于我们蛋白质调控的生物学假设的有效方法，包括鉴定上游调节因子和主要蛋白质节点。此外，蛋白质组学和计算机模拟数据与免疫组织化学和蛋白质印迹相结合，以鉴定一组代表某些选定通路的蛋白质，这些蛋白质在肌瘤、假包膜和正常子宫肌层样本中的表达失调。基于这些结果，我们证实了子宫肌瘤中细胞外基质成分、雌激素和孕激素受体的过度表达，并提出了可能与该肿瘤病理生理学相关的生物网络、经典通路和功能。
