Single-cell RNA sequencing reveals tumor cells and immune cells variation associated with lymphatic metastasis in papillary thyroid cancer

Background The biology of papillary thyroid carcinoma (PTC) is highly varied. However, the intraregional heterogeneity present in PTC with or without lymphatic metastasis (LM) is still not well understood. Methods 6 tumor samples from patients with PTC were used for viable cell scRNA-seq analysis. The cell types were identified using the markers from the CellMarker database and published research. To launch functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and Gene set enrichment analysis (GSEA) were carried out using ClusterProfiler. The Cell-Chat package was conducted to analyze the cell–cell interaction. Results 13 cell types were identified in the scRNA-seq dataset by published cell markers. Enrichment pathway analyses of tumor cells found that PTC with LM was associated with pathways related to cell proliferation, migration and survival. Cell–cell interaction analysis showed that the increased CD44-TYROBP-mediated and decreased PPIA-BSG and APP-SORL1-mediated cell communication between tumor cells and other cells.Specifically, CD8+ resident memory T cells emerged as pivotal regulators in LM of PTC, primarily through the expression of MHC-I, CD99 and LCK. Conclusions This study provides new insights into the heterogeneity of PTC and the basis for LM in PTC, which might provide potential therapeutic targets in future treatment.