Wang LingLing, Lv You, Li JinBin, Nan YongShan, Piao LongZhen, Liang ZheLong
Medical College of Yanbian University, Yanbian, Jilin, China.
Department of Anesthesia, Affiliated Hospital of Yanbian University, Yanbian, Jilin, China.
Histol Histopathol. 2023 Apr;38(4):467-474. doi: 10.14670/HH-18-535. Epub 2022 Oct 19.
To explore the correlation between the expression level of Desmoglein 2 (DSG2) and the epithelial-mesenchymal transition (EMT) progression in gallbladder cancer (GBC).
106 GBC tissue specimens and corresponding clinical information were collected to make a tissue microarray. Immunohistochemical method was used to test the expression level of DSG2 in GBC tissues. DSG2 was knocked down in the GBC cell line GBC-SD to detect the change of its invasion and metastasis ability. Then RT-qPCR and Western Blot were applied on the DSG2-knocked down GBC-SD cells to detect the expression level change of genes associated with EMT.
The high expression rate of DSG2 was significantly correlated with the N, M and TNM staging of patients (P<0.05). Survival analysis identified that GBC patients with high DSG2 expression level had significantly better survival (P<0.05). To further investigate the potential mechanism of DSG2 on regulating GBC tumor progression, we used knockdown DSG2 on GBC-SD cell lines. The results showed that GBC-SD cell lines with DSG2 knockdown showed a promotion of cell invasion and metastatic ability. The mRNA levels of EMT-related genes E-Cadherin, Snail, Twist, ZEB1, and β-catenin, which is a key protein in the Wnt signaling pathway, were also significantly altered. Besides, protein levels of E-cadherin and Snail showed consistent results.
The downregulation of DSG2 in gallbladder cancer is hypothesized to be associated with the invasion and metastasis progression of gallbladder cancer cells by regulating EMT-related pathways. Its expression level can be a novel biomarker for gallbladder cancer, providing new perspectives for diagnosis and treatment strategies.
探讨桥粒芯糖蛋白2（DSG2）表达水平与胆囊癌（GBC）上皮-间质转化（EMT）进程之间的相关性。
收集106例GBC组织标本及相应临床信息制作组织芯片。采用免疫组织化学方法检测GBC组织中DSG2的表达水平。在GBC细胞系GBC-SD中敲低DSG2，检测其侵袭和转移能力的变化。然后对敲低DSG2的GBC-SD细胞进行RT-qPCR和蛋白质免疫印迹，检测与EMT相关基因的表达水平变化。
DSG2的高表达率与患者的N、M及TNM分期显著相关（P<0.05）。生存分析表明，DSG2表达水平高的GBC患者生存情况明显更好（P<0.05）。为进一步研究DSG2调控GBC肿瘤进展的潜在机制，我们在GBC-SD细胞系中敲低DSG2。结果显示，敲低DSG2的GBC-SD细胞系的细胞侵袭和转移能力增强。EMT相关基因E-钙黏蛋白、Snail、Twist、ZEB1以及Wnt信号通路中的关键蛋白β-连环蛋白的mRNA水平也发生了显著变化。此外，E-钙黏蛋白和Snail的蛋白水平也呈现出一致的结果。
推测胆囊癌中DSG2的下调通过调节EMT相关途径与胆囊癌细胞的侵袭和转移进程相关。其表达水平可能成为胆囊癌的一种新型生物标志物，为诊断和治疗策略提供新的视角。
