CD27 exhibits clinical diagnostic value and reveals the immune heterogeneity as well as predicts clinical drug responses in hashimoto's thyroiditis

Abstract

Hashimoto's thyroiditis (HT), recognized as chronic lymphocytic thyroiditis, is a widespread autoimmune malady predominantly impacting females in the youthful and middle-age demographics. Initially, HT can present as hyperthyroidism, and as the disease progresses, it may transition to hypothyroidism. Studies have indicated that HT pathogenesis involves multiple factors, comprising genetic predisposition, environmental triggers, and autoimmune processes. However, the exact mechanism underlying the development of HT remains unclear. Within the framework of our study, we aimed to identify key genes and potential molecular mechanisms underlying HT, with the objective of offering fresh insights into diagnostic and therapeutic targets for this condition. To accomplish this, we amalgamated datasets GSE138198 and GSE54958 as our training cohorts, and subsequently conducted analyses encompassing the identification of differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) to pinpoint the DEGs most intricately associated with HT. Subsequently, we employed protein-protein interaction (PPI) network analysis to ascertain hub genes. We then proceeded to validate the diagnostic efficacy of these hub genes through the utilization of receiver operating characteristic (ROC) curves and nomograms. Finally, CD27 was selected as the key genes in HT and validated using clinical samples. More importantly, in order to delve deeper into the role and potential mechanisms associated with CD27 in HT, we conducted a comprehensive array of analyses including GO, KEGG and GSEA enrichment analysis, and HT-infiltrating immune cells (HTICs) components as well as functions were performed between high CD27 and low-CD27 cohorts. The findings revealed that CD27 is highly expressed in HT tissues and has important clinical application value for HT. The CD27 expression in high-cohort exhibited a more pronounced enrichment in immune-related biological processes compared to the low-expression cohort. Furthermore, we conducted CIBERSORT analysis to assess the proportion of HTICs, revealing a strong association between several activated HTICs and CD27 expression. This implies that CD27 has the potential to serve as an indicator of the immune status in individuals with Hashimoto's thyroiditis. Consequently, CD27 plays a significant role in predicting clinical outcomes in HT patients, encompassing the overall condition of HT patients and their response to immunotherapy. Furthermore, CD27 holds promise as a valuable biomarker for reshaping the microenvironment in Hashimoto's thyroiditis. This suggests potential underlying mechanisms contributing to the pathogenesis and progression of HT. Such insights may offer novel perspectives for HT treatment, ultimately leading to enhanced therapeutic strategies and improved patient care.