Research Identifies Key Genes Linking Hashimoto Thyroiditis and Papillary Thyroid Carcinoma

Researchers identified multiple shared biomarkers that reinforce the association between papillary thyroid carcinoma (PTC) and Hashimoto thyroiditis (HT), according to their findings published in Scientific Reports.

The inflammatory environment created by HT may establish an advantageous setting for the formation and proliferation of malignant cells. Image Credit: © Graphicroyalty - stock.adobe.com

HT is an autoimmune disorder in which the immune system releases lymphocytes and autoantibodies targeting antigens to attack the thyroid gland, resulting in the death of hormone-producing cells and the subsequent decline in hormone production, commonly referred to as hypothyroidism. The causal mechanism underlying the immune system attacking the thyroid is not well understood. However, the onset of disease may be related to genetic factors and environmental triggers, such as infection, stress, or radiation exposure. HT can occur in anyone but is more prevalent among middle-aged women.^1,2

PTC is the most common thyroid cancer, making up about 80% of all cases and is the 8th most common cancer among women under the age of 25 years. Most patients will not know they have PTC because it is often asymptomatic. The most common symptom that leads to diagnosis is the presence of palpable or visible masses that may cause difficulty swallowing, and pressure or shortness of breath when lying flat. According to prior findings, PTC occurs in approximately 33% of patients with HT.^1-3

It is well understood in the scientific community that chronic inflammation and autoimmune diseases increase the risk of cancer. Years of research continue to reinforce the association between HT and the occurrence or development of PTC, finding they have some shared clinical and histopathological features. This indicates that HT might act as a stand-alone factor contributing to the development of PTC. The inflammatory environment created by HT may establish an advantageous setting for the formation and proliferation of malignant cells; however, the molecular mechanisms underlying the transformation of HT to PTC remain unclear and require continued study.²

The researchers aimed to identify potential biomarkers that may be associated with both PTC and HT, which could inform the development of advanced diagnostic and therapeutic targets that address these shared genetic factors. They collected 3 microarray datasets from the GEO database and an RNA-sequencing (RNA-seq) dataset from the TCGA database to identify shared differentially expressed genes (DEGs) between HT and PTC.²

Using random forest algorithms, the researchers focused on three key hub genes—CD53, FCER1G, and TYROBP—for the development of three diagnostic models: the artificial neural network, EXtreme Gradient Boosting, and Decision Tree models. The Human Protein Atlas database and immunofluorescence staining were used for validating the protein expressions of the hub genes.²

The protein–protein interaction analysis revealed 6 significant modules comprising a total of 29 genes. Microarray and RNA-seq datasets were used to identify 101 DEGs with specific involvement in inflammation- and immune-related signaling pathways, with CD53, FCER1G, and TYROBP being critical in the development and progression of both HT and PTC. The researchers hypothesize that benzylpenicilloyl polylysine and aspirin may be effective in targeting inflammatory processes and immune responses to treat HT and PTC and may prevent the progression from HT to PTC.²

The findings are significant for enhancing the clinical understanding and pathophysiological mechanisms of HT, as well as its relationship to PTC. The results may inform the development of diagnostic methods and therapeutic treatments for patients with HT or PTC, offering advanced options to prevent or manage the progression of these diseases.

References

1. Hashimoto’s disease. Mayo Clinic. January 15, 2022. Accessed August 9, 2024. https://www.mayoclinic.org/diseases-conditions/hashimotos-disease/symptoms-causes/syc-20351855

2. Jiang H, He Y, Lan X, et al. Identification and validation of potential common biomarkers for papillary thyroid carcinoma and hashimoto’s thyroiditis through bioinformatics analysis and machine learning. Sci Rep. July 6, 2024. doi:10.1038/s41598-024-66162-2

3. Papillary thyroid cancer. Columbia. Accessed August 9, 2024. https://columbiasurgery.org/conditions-and-treatments/papillary-thyroid-cancehttps://columbiasurgery.org/conditions-and-treatments/papillary-thyroid-cance