Single-cell RNA sequencing reveals tumor cell and immune cell variations 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: Six tumor samples from patients with PTC were used for viable cell single-cell RNA sequencing (scRNA-seq) analysis. The cell types were identified using markers from the CellMarker database and published research. To perform 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 used 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 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.