Department of Gastroenterology, Linyi County People's Hospital, Dezhou, China.
Laboratory of Urology and Andrology, Jiangsu Clinical Medicine Research Institution, Nanjing, China.
Front Immunol. 2023 Sep 21;14:1239875. doi: 10.3389/fimmu.2023.1239875. eCollection 2023.
Cadherin 5 (CDH5) functions critically in maintaining cell adhesion and integrity of endothelial and vascular cells. The expression of CDH5 is abnormal in tumor cells, which may have great potential to serve as a new immune checkpoint. The current pan-cancer analysis was performed to better understand the role of CDH5 in tumor.
The clinical significance and immunological function of CDH5 in pan-cancers were comprehensively analyzed based on the correlations between CDH5 and clinicopathologic features, prognosis values, tumor mutation burden (TMB), microsatellite instability (MSI), immune cells infiltration and immune response genes using 33 datasets from The Cancer Genome Atlas (TCGA). We further confirmed the expression of CDH5 in bladder cancer (BCa) tissues and cell lines. The CD8 T cells were screened from peripheral blood of healthy controls and activated. BCa cell-CD8 T cell co-culture assay and ELISA assay were carried out to verify the immunological function of CDH5.
The expression of CDH5 was down-regulated in 8 types of tumors including in BCa but up-regulated in 4 types of tumors. CDH5 was significantly correlated with tumor stage in 6 types of tumors. In addition, CDH5 was positively or negatively correlated with tumor prognosis. Furthermore, CDH5 was closely associated with TMB in 15 types of tumors and with MSI in 9 types of tumors. KEGG-GSEA and Hallmarks-GSEA analyses results indicated that CDH5 was positively related to immune response in most tumor types. In many tumors, CDH5 showed a positive correlation with immune cell infiltration. Enrichment analyses demonstrated that CDH5 was significantly related to the expression of many immunomodulators and chemokines. Further experiments showed that CDH5 was low-expressed in BCa tissues and cell lines in comparison to adjacent normal tissues and normal urothelial cell line, but it was positively associated with a better prognosis of BCa patients. The results of co-culture assay and ELISA assay demonstrated that CDH5 could promote the function of CD8 T cells in TME of BCa.
In summary, CDH5 was positively associated with a favorable prognosis and effective immune response in tumors, showing a great potential to serve as a novel tumor biomarker and immune checkpoint.
钙黏蛋白 5（CDH5）在维持内皮细胞和血管细胞的细胞黏附和完整性方面起着至关重要的作用。肿瘤细胞中 CDH5 的表达异常，这可能使其具有成为新的免疫检查点的巨大潜力。目前进行了泛癌分析，以更好地了解 CDH5 在肿瘤中的作用。
基于 CDH5 与临床病理特征、预后价值、肿瘤突变负担（TMB）、微卫星不稳定性（MSI）、免疫细胞浸润和免疫反应基因之间的相关性，利用来自癌症基因组图谱（TCGA）的 33 个数据集，全面分析了 CDH5 在泛癌中的临床意义和免疫功能。我们进一步证实了 CDH5 在膀胱癌（BCa）组织和细胞系中的表达。从健康对照者的外周血中筛选 CD8 T 细胞并进行激活。进行 BCa 细胞-CD8 T 细胞共培养实验和 ELISA 实验，以验证 CDH5 的免疫功能。
在包括膀胱癌在内的 8 种肿瘤中，CDH5 的表达下调，但在 4 种肿瘤中上调。在 6 种肿瘤中，CDH5 与肿瘤分期显著相关。此外，CDH5 与肿瘤预后呈正相关或负相关。此外，在 15 种肿瘤中，CDH5 与 TMB 密切相关，在 9 种肿瘤中与 MSI 相关。KEGG-GSEA 和 Hallmarks-GSEA 分析结果表明，在大多数肿瘤类型中，CDH5 与免疫反应呈正相关。在许多肿瘤中，CDH5 与免疫细胞浸润呈正相关。富集分析表明，CDH5 与许多免疫调节剂和趋化因子的表达显著相关。进一步的实验表明，与相邻正常组织和正常尿路上皮细胞系相比，CDH5 在膀胱癌组织和细胞系中表达较低，但与膀胱癌患者的良好预后呈正相关。共培养实验和 ELISA 实验的结果表明，CDH5 可促进膀胱癌肿瘤微环境中 CD8 T 细胞的功能。
综上所述，CDH5 与肿瘤的良好预后和有效免疫反应呈正相关，具有成为新的肿瘤标志物和免疫检查点的巨大潜力。
