Placental-Cadherin, a biomarker for local immune status and poor prognosis among patients with tongue squamous cell carcinoma.

BACKGROUND

The prognostic and clinicopathological value of placental-Cadherin (CDH3) in multiple cancers is controversial. The diagnostic significance and functional mechanism of CDH3 in tongue squamous cell carcinoma (TSCC) have not been thoroughly investigated. This study aims to clarify the potential of CDH3 as biomarker for TSCC.

METHODS

Here, meta-analysis, bioinformatics, along wet-lab techniques were employed to evaluate the diagnostic, as well as the prognostic value of CDH3 in diverse types of cancers, especially TSCC. Meta-analysis was used to determine the influence of CDH3 on prognostic and clinicopathological features in numerous cancers. Molecular biology function was used to investigate the role of CDH3 in TSCC cells. The relationship of CDH3 with tumor-infiltrating immune cells (TIICs) in TSCC was assessed using CIBERSORT. Moreover, gene set enrichment analysis (GSEA) was done based on TCGA. Besides, the hub genes and associated cascades were uncovered based on gene co-expression with CDH3.

RESULTS

CDH3 upregulation correlated with worse overall survival and disease-free survival in various cancers. CDH3 was validated as an independent risk factor for HNSC and was linked to the onset of tumors, tumor stage, and infiltration depth. CDH3 silencing inhibited cell growth and induced apoptosis of the CAL-27 cell line. CDH3 expression level correlated with infiltration by macrophages, T cells, T cell regulatory cells (Tregs), and plasma cells in TSCC. GSEA revealed that CDH3 influences multiple cancer-associated cascades. Besides, CBX3, CCHCR1, along NFYC were identified as the core hub genes for CDH3.

CONCLUSION

We identified CDH3 as a pan-cancer gene with potential prognostic and diagnostic significance in various cancers, particularly in TSCC, where it is tumorigenic.