Explore the possible influence of Sjogren's syndrome on thyroid cancer: A literature data mining and meta-analysis

To explore the potential influence of Sjogren's syndrome (SS) on thyroid cancer (TC).

First, a literature data mining (LDM) approach was used to reconstruct functional pathways connecting SS and TC. A meta-analysis was then performed to examine the expression changes of genes mediated by SS using 16 TC case/control expression datasets, with results validated through the TCGA/GTEx dataset. Finally, gene set enrichment analysis (GSEA) and survival analysis using GEPIA2 were conducted on the significant genes.

Our findings indicate that SS may increase the risk of TC by activating 14 TC promoters (PDCD1, NTRK1, LGALS3, CD274, FOXP3, BCL2, CYP1A1, HMGB1, TGFB1, CCL2, PLA2G7, TFF3, LCN2, and CLDN1) and suppressing three TC inhibitors (MIR145, MIR30C1, and EP300). Four molecules (PLA2G7, TFF3, LCN2, and CLDN1) exhibited significant expression changes in TC patients (LFC > 1 or < -1; p < 2.07E-04), which were confirmed in TCGA/GTEx expression analysis. These results highlight three possible mechanisms-the SS-PLA2G7-CCL2-TC pathway, the SS-LCN2-LGALS3-TC pathway, and the SS-CLDN1-BCL2-TC pathway-that may explain how SS contributes to TC development. Enrichment analysis suggests that SS may affect TC prognosis by regulating leukocytes and tolerance induction. Survival analysis indicates that SS may enhance TC survival through the regulation of the CLDN1 and EGF pathways.

LDM-based pathway analysis highlighted three genetic pathways through which SS may adversely affect TC progression, while SS may enhance TC survival via the CLDN1 and EGF pathways, highlighting the need for further research.