首页|基于高通量蛋白质组学分析的皮肤衰老与皮肤鳞状细胞癌发生的相关机制研究

基于高通量蛋白质组学分析的皮肤衰老与皮肤鳞状细胞癌发生的相关机制研究

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目的 研究年轻人、老年人正常皮肤和老年皮肤鳞状细胞癌(cutaneous squamous cell carcinoma,cSCC)患者的cSCC皮肤组织蛋白质组学变化,寻找与皮肤衰老和cSCC相关的蛋白质标志物,为cSCC治疗的靶向筛选提供新依据.方法 选取四川大学华西医院2019年1月-2020年12月的5例老年cSCC患者皮肤组织样本和10例手术中切除的正常皮肤组织样本(年轻人和老年人皮肤样本各5例).通过苏木精-伊红染色观察组织形态结构差异,用压力循环技术定性和定量分析全蛋白质组.结果 与年轻人相比,老年人皮肤组织结构和组成成分发生相应的变化,包括皮肤组织变薄,胶原密度增加以及胶原排列更加整齐;与正常皮肤相比,cSCC组织表皮细胞异型增生,核分裂异常,细胞排列呈癌巢状,伴有炎症细胞浸润和角化珠形成.全蛋白质组学分析鉴别出3008种特异性蛋白,其中37种为共同差异蛋白.进一步筛查数据库发现,其中8种蛋白来自细胞外基质,主要参与形态结构形成、抗拉强度、与血小板源性生长因子及受体的相互作用、胶原分解代谢和细胞黏附作用等.结论 衰老导致皮肤结构发生了改变,衰老所导致的组织结构变化导致皮肤屏障功能减弱.同时衰老导致在细胞外基质中具有抑制肿瘤进展功能的蛋白表达下调,而具有促进肿瘤进展功能的蛋白表达上调.这些改变可能通过影响肿瘤细胞外微环境的调节机制,进而影响cSCC的发生与发展.
Related mechanism between skin aging and occurrence of cutaneous squamous cell carcinoma:a high-throughput proteomics-based analysis
Objective To investigate the proteomic changes among normal skin tissues in young and elderly people and cutaneous squamous cell carcinoma(cSCC)tissues in elderly patients with cSCC,find proteins associated with skin aging and cSCC,and provide a new basis for target screening for cSCC therapy.Methods Five cSCC tissue samples from 5 elderly patients with cSCC and 10 normal skin tissue samples from 5 young and 5 elderly people removed during surgery between January 2019 and December 2020 in West China Hospital of Sichuan University were selected.The differences in tissue morphology and structure were observed by hematoxylin-eosin staining,and the whole protein group was qualitatively and quantitatively analyzed by pressure cycle technique.Results With aging,the structure of skin tissues underwent corresponding changes,including thinning of the skin,increased collagen fiber density,and more organized arrangement.Compared to normal skin tissue,cSCC tissue exhibited epithelial cell dysplasia,atypical mitoses,nest-like distribution of cancer cells,infiltration of inflammatory cells,and formation of keratin pearls.Proteomic analysis identified 3 008 specific proteins,and there were 37 proteins with common differential expression.Further screening of databases identified 8 proteins derived from the extracellular matrix,primarily involved in morphological structure formation,tensile strength,interaction with platelet-derived growth factors and receptors,collagen degradation metabolism,and cell adhesion.Conclusions Aging leads to changes in skin structure.The changes of tissue structure caused by aging lead to the weakening of skin barrier function.At the same time,aging leads to the down-regulated expression of protein with the function of inhibiting tumor progression and the up-regulated expression of protein with the function of promoting tumor progression in extracellular matrix.These changes may affect the occurrence and development of cSCC by affecting the regulation mechanism of tumor extracellular microenvironment.

Cutaneous squamous cell carcinomaagingproteomicsextracellular matrix

张师玮、陈俊杰

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四川大学华西医院整形外科/烧伤科(成都 610041)

皮肤鳞状细胞癌 衰老 蛋白质组学 细胞外基质

四川省科技计划

2020YSF0267

2024

华西医学
四川大学华西医院

华西医学

CSTPCD
影响因子:0.744
ISSN:1002-0179
年,卷(期):2024.39(5)
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