Comparative Transcriptomic Analysis of Pathogenic Mechanisms in Papillary Thyroid Carcinoma and Hashimoto's Thyroiditis

Purpose Papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT) are diseases where one is a "cancer" that has escaped immune system surveillance, and the other is an "autoimmune disease" that attacks the body's own systems. They appear to be antagonistic in form, but in reality, they can occur simultaneously. The similarities or differences in their gene molecular expression are worth in-depth discussion. Research Methods This study searched the GEO database, integrating 4 GEO datasets to compare the gene expression similarities and differences in thyroid tissues of papillary thyroid carcinoma (PTC), Hashimoto's thyroiditis (HT), and concurrent PTC and HT (PTC_HT) against normal tissue (Control). The limma software package was used to select differentially expressed genes compared to normal tissue (Control), followed by KEGG clustering and gene pathway interaction analysis. Finally, we verified the differentially expressed genes discovered in our collected PTC, HT, and adjacent cancer tissues. Results We integrated and analyzed gene expression data from 166 tissue samples in the database, finding 202 genes with significant expression differences in PTC, HT, and PTC_HT pathological phenotypes. Moreover, these 202 genes showed consistent expression trends (i.e., same direction of increase or decrease) in the cells of the three pathological phenotypes. They are mainly inflammatory and chemokine factors (CXCL8, CXCL9, CXCL10, and IL8), with thyroid cells in all three diseases existing in an environment where chemokines activate inflammation. They also do not respond to p53 and FAS-induced apoptosis signals. Comparing genes with completely opposite expression trends between PTC and HT, we found these genes mainly concentrated in the ECM-receptor interaction pathway, involving genes such as FN1, LAMB1, and LAMC1. By combining DEGs and hubGenes, we found that differences in the FN1-DUSP6-ETV5-NFATC1/3 signaling axis may be the cause of different phenotypes in HT and PTC. QPCR and WB verification of collected PTC, HT, and adjacent cancer patient tissues also supported these findings. Conclusion Based on the above results, we believe that cells in both PTC and HT are in a state of chronic inflammatory activation and do not respond to p53 and FAS-induced apoptosis signals. Chronic inflammation may promote apoptosis non-response. The molecular expression differences between PTC and HT mainly focus on the expression differences in the extracellular matrix, which activate/inhibit T cell immune responses, leading to different disease phenotypes.