Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Obstetrics and Gynecology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Pathol Res Pract. 2024 Oct;262:155554. doi: 10.1016/j.prp.2024.155554. Epub 2024 Aug 23.
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.
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.
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.
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.
桥粒芯糖蛋白 2（DSG2）在各种疾病中发挥着关键作用。然而，其在宫颈癌（CC）中的作用仍未得到充分阐明。在这里，我们旨在使用生物信息学和实验方法全面探讨 DSG2 在 CC 中的功能机制。
使用多个在线数据库，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，来探讨 DSG2 在 CC 中的表达、预后、基因突变和潜在信号通路。使用定量实时 PCR（qRT-PCR）和蛋白质印迹法（western blotting）来测量收集样本中的 DSG2 表达。进行实验来验证失调的 DSG2 对体外宫颈细胞系的影响。
生物信息学分析显示，DSG2 在 CC 中的 mRNA 和蛋白水平均显著上调。升高的 DSG2 水平也与预后不良和临床参数（如癌症分期、肿瘤分级、淋巴结转移状态等）相关。DSG2 表达主要在上皮细胞中观察到，在单细胞分辨率上随着疾病的进展而增加。此外，上调 DSG2 通过减少免疫细胞（如 B 细胞、T 细胞、NK 细胞等）的浸润显著提高了肿瘤纯度。在收集的 CC 样本中，DSG2 的过表达在 mRNA 和蛋白水平上均得到验证。DSG2 的敲低显著降低了 CC 细胞系在体外的增殖和侵袭。
总之，DSG2 水平升高与 CC 中的不良预后和免疫浸润减少显著相关。因此，DSG2 可能成为 CC 的潜在治疗和诊断生物标志物。
