Background

CDH3 is a glycoprotein with a single-span transmembrane domain that mediates cell-to-cell adhesion. Abnormal expression of CDH3 is associated with a poor prognosis in patients with breast, thyroid, colorectal carcinomas and glioblastoma. Soluble CDH3 in pleural effusions can be used as a marker for real-time monitoring of resistance to first- and second-generation EGFR-TKIs. The CDH3 mechanism underlying lung adenocarcinomas (LUADs) has not been established.

Objective

This study analyzed the correlation between CDH3 expression and lung cancer prognosis and the effect of down-regulation CDH3 expression on the proliferation and migration of lung cancer cells.

Methods

CDH3 expression was studied using the Oncomine, TIMER, PanglaoDB, and GEPIA databases. The effect of CDH3 on clinical prognosis was assessed with GEPIA, the PrognoScan database, and Kaplan–Meier plotter. The relationship between CDH3 to immune infiltrating cells was explored using TIMER and TISIDB. The function of CDH3 in lung cancer cell lines was determined by CCK-8 and wound healing assays in vitro. Furthermore, RNA sequencing was used to identify key signaling pathways and differentially-expressed genes.

Results

LUAD tissues had higher CDH3 expression compared with normal tissues and were associated with worse overall survival in patients with LUAD. CDH3 expression had positive associations with infiltration of CD4 + T cells, Tregs and exhausted T cells, but negative associations with infiltration of B cells in patients with LUAD. CCK-8 and wound healing assays revealed that downregulation of CDH3 inhibited the proliferation and migration of cells. KEGG analysis revealed that the TGF-beta signaling pathways were demonstrated to be enriched pathways for genes negatively regulated by knockdown of CDH3.

Conclusion

CDH3 expression affects proliferation and migration of lung cancer cells and might serve as a potential prognostic marker in LUAD patients.

中文翻译：

---

CDH3 下调与 LUAD 的更好预后相关，并减少肺癌细胞的增殖和迁移

背景

CDH3是一种具有单跨跨膜结构域的糖蛋白，可介导细胞间粘附。CDH3的异常表达与乳腺癌、甲状腺癌、结直肠癌和胶质母细胞瘤患者的不良预后相关。胸腔积液中的可溶性CDH3可作为实时监测第一代和第二代EGFR-TKI耐药性的标志物。肺腺癌 (LUAD) 的CDH3机制尚未确定。

客观的

本研究分析了CDH3表达与肺癌预后的相关性以及下调CDH3表达对肺癌细胞增殖和迁移的影响。

方法

使用 Oncomine、TIMER、PanglaoDB 和 GEPIA 数据库研究CDH3表达。使用 GEPIA、PrognoScan 数据库和 Kaplan-Meier 绘图仪评估CDH3对临床预后的影响。使用 TIMER 和 TISIDB 探讨了CDH3与免疫浸润细胞之间的关系。 CDH3在肺癌细胞系中的功能通过 CCK-8 和体外伤口愈合测定来确定。此外，RNA测序用于识别关键信号通路和差异表达基因。

结果

与正常组织相比，LUAD 组织具有更高的CDH3表达，并且与 LUAD 患者较差的总生存率相关。在 LUAD 患者中，CDH3表达与 CD4+T 细胞、Treg 细胞和耗竭 T 细胞的浸润呈正相关，但与 B 细胞浸润呈负相关。 CCK-8和伤口愈合测定表明CDH3的下调抑制了细胞的增殖和迁移。 KEGG 分析显示，TGF-β 信号通路被证明是通过敲低CDH3 负调控基因的富集通路。

结论

CDH3表达影响肺癌细胞的增殖和迁移，并可能作为 LUAD 患者的潜在预后标志物。