Consistent analysis of differentially expressed genes across 7 cell types in papillary thyroid carcinoma

Single-cell transcriptome sequencing (scRNA-seq) provides a higher resolution of cellular differences than bulk RNA-seq, enabling the dissection of cell-type-specific responses to perturbations in papillary thyroid carcinoma (PTC). However, cellular genomic features are highly heterogeneous and have a large number of genes without any expression signals, which hinders the statistical power to identify differentially expressed genes and may generate many false-positive results. To overcome this challenge, we conducted an integrative analysis on two PTC scRNA-seq datasets and cross-validated consistent differential expression. By combining results from 32 common cell types in the two studies, we identified 31 consistently differentially expressed genes (DEGs) across seven cell types, including B cells, endothelial cells, epithelial cells, monocytes, NK cells, smooth muscle cells, and T cells. Functional enrichment analysis revealed that these genes are important for the adaptive immune response and autoimmune thyroid diseases. The additional disease-free survival analysis also confirmed that these 31 genes significantly affected patient survival time in large scale thyroid cancer cohort. Furthermore, we experimentally validated one of the top consistent DEGs as a potential biomarker gene of PTC epithelial cells, KRT7, which may be a upstream gene for the NF-κB signaling pathway. The result shows that KRT7 may promote thyroid cancer metastasis through the epithelial-mesenchymal transition and NF-κB signaling pathway. In summary, our single-cell transcriptome integration-based approach may provide insights into the important role of NF-κB in the underlying biology of the PTC.