A novel prognostic signature and immune microenvironment characteristics associated with disulfidptosis in papillary thyroid carcinoma based on single-cell RNA sequencing

Abstract

Background: Disulfidptosis is a newly discovered form of regulated cell death. The research on disulfidptosis and tumor progression remains unclear. Our research aims to explore the relationship between disulfidptosis-related genes (DRGs) and the clinical outcomes of papillary thyroid carcinoma (PTC), and its interaction on the tumor microenvironment. Methods: The single-cell RNA seq data of PTC was collected from GEO dataset GSE191288. We illustrated the expression patterns of disulfidptosis-related genes in different cellular components in thyroid cancer. LASSO analyses were performed to construct a disulfidptosis associated risk model in TCGA-THCA database. GO and KEGG analyses were used for functional analyses. CIBERSORT and ESTIMATE algorithm helped with the immune infiltration estimation. qRT‒PCR and flow cytometry was performed to validate the hub gene expression and immune infiltration in clinical samples. Results: We clustered PTC scRNA seq data into 8 annotated cell types. With further DRGs based scoring analyses, we found endothelial cells exhibited the most relationship with disulfidptosis. A 4-gene risk model was established based on the expression pattern of DRGs related endothelial cell subset. The risk model showed good independent prognostic value in both training and validation dataset. Functional enrichment and genomic feature analysis exhibited the significant correlation between tumor immune infiltration and the signature. The results of flow cytometry and immune infiltration estimation showed the higher risk scores was related to immuno-suppressive tumor microenvironment in PTC. Conclusion: Our study exhibited the role of disulfidptosis based signature in the regulation of tumor immune microenvironment and the survival of PTC patients. A 4-gene prognostic signature (including SNAI1, STC1, PKHD1L1 and ANKRD37) was built on the basis of disulfidptosis related endothelial cells. The significance of clinical outcome and immune infiltration pattern was validated robustly.

Keywords: disulfidptosis; endothelial cells; immune infiltration; papillary thyroid carcinoma; prognostic signature.