Analysis of single-cell RNA sequencing data revealed the upregulation of Wnt signaling pathway and potential biomarkers in Oral Squamous Cell Carcinoma cancer-associated fibroblasts

Original Research


Background: CAFs (cancer-associated fibroblasts) and tumor-associated p-EMT (partial epithelial mesenchymal transition) cells coexist and contribute to the formation of epithelial tumors like OSCC (oral squamous cell carcinoma). In oral cancer, Wnt signaling pathway contributes to the tumor progression, invasion and metastasis. Here we deeply analyzed Wnt signaling pathway using our previous single-cell RNA-seq data of CAFs and p-EMT tumor cells in OSCC by computational methods.

Material and methods: Integrated single-cell RNA sequencing data of OSCC CAF and p-EMT clusters were obtained from our previous study. These cells were from samples being primary tumor, oral cavity location, metastasis information and then analyzed by R, Python to investigate the gene expression, cell-cell communication, gen set enrichment analysis (GSEA) and overall survival analysis across metastasis conditions regarding Wnt signaling pathway.

Results: Genes related to Wnt signaling pathway upregulated in CAFs and p-EMT cancer cells, especially under metastasis condition including WNT2, WNT5A, FZD1-4, ROR2 in CAFs, and WNT7B, FZD2/5/6 in p-EMT cells. Cell-cell interaction analysis and GSEA in CAFs and p-EMT tumor cells highlighted non-canonical Wnt signaling pathway in CAFs and canonical Wnt signaling pathway in p-EMT tumor cells. CTHRC1 and SFRP2 were suggested as biomarkers in Wnt signaling pathway of CAFs from the gene expression, GSEA and overall survival analysis.

Conclusion: Our study found CTHRC1 and SFRP2 as biomarkers for HSCC and OSCC prognosis belong to CAFs of TME. It might pave the way for targetable treatment based on WNT ligand-receptor interaction and Wnt signaling modulation in OSCC CAFs based on metastatic status.

Graphical abstract