Integrated Multi-Omics and Single-Cell Analyses Identify PCDHGB4 as a Prognostic Biomarker and Oncogenic Regulator in Pan-Squamous Cell Carcinoma

Abstract

Background

Protocadherin gamma subfamily B member 4 (PCDHGB4) encodes a protein associated with wound healing; however, its role in pan-cancer, particularly in squamous cell carcinoma (SCC), remains unclear.

Methods

TCGA data were used to assess the prognostic value and mutation characteristics of PCDHGB4. Single-cell and spatial transcriptomics analyses were performed to examine its expression patterns. Functional roles were evaluated using in vitro proliferation and metastasis assays, along with overexpression and knockdown experiments in SCC cell lines.

Results

PCDHGB4 was identified as a prognostic biomarker in SCC. Its alterations were associated with patient survival across cancers. Single-cell analyses revealed that PCDHGB4 expression is enriched in malignant cells and is associated with tumor progression. Immune infiltration analysis suggested a suppressive effect on immune cell distribution in SCC. Pathway analyses indicated activation of oncogenic signaling, and experimental validation confirmed that PCDHGB4 regulates the PI3K-AKT pathway in SCC cells.

Conclusion

PCDHGB4 is a potential biomarker for pan-cancer, especially SCC, and may promote tumor progression through oncogenic signaling and modulation of the tumor immune microenvironment.