背景:据报道,Desmoglein-2(DSG2)在各种疾病中起关键作用。然而,其在宫颈癌(CC)中的作用仍未得到充分阐明。这里,本研究采用生物信息学和实验方法全面探讨DSG2在CC中的作用机制。
方法:几个在线数据库,包括基因表达谱交互式分析(GEPIA),ONCOMINE,LinkedOmics,MetaScape,人类蛋白质图谱(HPA),OMICS和单细胞RNA测序(scRNA-seq)数据用于探索表达,预后,基因突变,以及CC中DSG2的潜在信号通路。使用定量实时PCR(qRT-PCR)和蛋白质印迹来测量收集的样品中的DSG2表达。进行实验测定以验证失调的DSG2在体外对宫颈细胞系的影响。
结果:生物信息学分析显示,在mRNA和蛋白水平上,与正常宫颈组织相比,CC中的DSG2显著上调。升高的DSG2水平也与不良预后和临床参数相关(例如,癌症阶段,肿瘤分级,淋巴结转移状态,等。).DSG2表达主要在上皮细胞中观察到,随着单细胞分辨率的疾病进展而增加。此外,DSG2的上调通过减少免疫细胞的浸润显着提高肿瘤纯度(例如,B细胞,T细胞,NK细胞,等。).在mRNA和蛋白质水平的收集的CC样品中进一步验证了DSG2的过表达。体外敲除DSG2可显著降低CC细胞系的增殖和侵袭能力。
结论:总之,升高的DSG2水平与CC的不良预后和免疫浸润减少显著相关.因此,DSG2可作为CC的潜在治疗和诊断生物标志物。
BACKGROUND: Desmoglein-2 (DSG2) has been reported to play pivotal roles in various diseases. However, its roles in cervical cancer (CC) remain insufficiently elucidated. Here, we aimed to comprehensively explore the functional mechanisms of DSG2 in CC using bioinformatics and experimental methods.
METHODS: Several online databases, including Gene Expression Profiling Interactive Analysis (GEPIA), ONCOMINE, LinkedOmics, MetaScape, Human protein atlas (HPA), OMICS and single-cell RNA sequencing (scRNA-seq) data were used to explore the expression, prognosis, gene mutations, and potential signaling pathway of DSG2 in CC. Quantitative real-time PCR (qRT-PCR) and western blotting were used to measure DSG2 expression in collected samples. Experimental assays were conducted to verify the effects of dysregulated DSG2 on cervical cell lines in vitro.
RESULTS: Bioinformatic analyses revealed that DSG2 was significantly up-regulated in CC compared to normal cervical tissues at both mRNA and protein levels. Elevated DSG2 levels were also associated with poor prognosis and clinical parameters (e.g., cancer stages, tumor grade, nodal metastasis status, etc.). DSG2 expression was predominantly observed in epithelial cells, increasing with disease progression on a single-cell resolution. Additionally, up-regulation of DSG2 significantly enhanced tumor purity by reducing the infiltration of immune cells (e.g., B cells, T cells, NK cells, etc.). Over-expression of DSG2 was further validated in collected CC samples at both mRNA and protein levels. Knockdown of DSG2 markedly reduced the proliferation and invasion of CC cell lines in vitro.
CONCLUSIONS: In summary, elevated levels of DSG2 were significantly associated with poor prognosis and diminished immune infiltration in CC. Thus, DSG2 may serve as a potential therapeutic and diagnostic biomarker for CC.