Genetic relationship between Hashimoto`s thyroiditis and papillary thyroid carcinoma with coexisting Hashimoto`s...

Area of Science:

• Endocrinology and Oncology
• Genetics and Molecular Biology

Background:

• Hashimoto's thyroiditis (HT) is found in approximately 30% of papillary thyroid carcinomas (PTCs).
• The genetic basis for HT's predisposition to PTC is not fully understood.

Purpose of the Study:

• To analyze gene expression profiles in HT and PTC to identify shared genetic alterations.
• To investigate the role of immune response, oxidative stress, and DNA repair genes in the co-occurrence of HT and PTC.

Main Methods:

• Microarray analysis of gene expression in normal thyroid, HT, PTC with HT, PTC without HT, and micro PTC samples.
• Differential gene expression analysis using FDR-adjusted p-value ≤ 0.05 and fold change > 2.
• Venn diagram analysis to identify shared and unique differentially expressed genes (DEGs) across comparison groups.

Main Results:

• A set of 71 shared DEGs between HT and PTC with HT samples showed significant enrichment in immune/inflammatory functions, oxidative stress, DNA damage/repair, cell cycle, and apoptosis.
• The majority of these 71 DEGs were upregulated, including immunoglobulin kappa variable genes, CD86, IL2RG, IFI6, STAT1, MMP9, TOP2A, and BRCA2.
• Further analysis identified distinct DEG sets specific to HT and the intersection of all groups, highlighting complex genetic deregulation.

Conclusions:

• Genes related to immune response, inflammation, oxidative stress, DNA damage/repair, cell cycle, and apoptosis are deregulated in samples co-affected by HT and PTC.
• These findings support a model where chronic inflammation in HT may contribute to oncogenic transformation in PTC through genetic deregulation.
• The identified DEGs represent potential candidate genes and biomarkers for clinical applications in thyroid cancer research.