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Identifying and analyzing the key genes shared by papillary thyroid carcinoma and Hashimoto’s thyroiditis using bioinformatics methods

BACKGROUND: Hashimoto’s thyroiditis (HT) is a chronic autoimmune disease that poses a risk factor for papillary thyroid carcinoma (PTC). The present study aimed to identify the key genes shared by HT and PTC for advancing the current understanding of their shared pathogenesis and molecular mechanism...

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Autores principales: Liu, Ting-ting, Yin, De-tao, Wang, Nan, Li, Na, Dong, Gang, Peng, Meng-fan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266228/
https://www.ncbi.nlm.nih.gov/pubmed/37324256
http://dx.doi.org/10.3389/fendo.2023.1140094
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author Liu, Ting-ting
Yin, De-tao
Wang, Nan
Li, Na
Dong, Gang
Peng, Meng-fan
author_facet Liu, Ting-ting
Yin, De-tao
Wang, Nan
Li, Na
Dong, Gang
Peng, Meng-fan
author_sort Liu, Ting-ting
collection PubMed
description BACKGROUND: Hashimoto’s thyroiditis (HT) is a chronic autoimmune disease that poses a risk factor for papillary thyroid carcinoma (PTC). The present study aimed to identify the key genes shared by HT and PTC for advancing the current understanding of their shared pathogenesis and molecular mechanisms. METHODS: HT- and PTC-related datasets (GSE138198 and GSE33630, respectively) were retrieved from the Gene Expression Omnibus (GEO) database. Genes significantly related to the PTC phenotype were identified using weighted gene co-expression network analysis (WGCNA). Differentially expressed genes (DEGs) were identified between PTC and healthy samples from GSE33630, and between HT and normal samples from GSE138198. Subsequently, functional enrichment analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Transcription factors and miRNAs regulating the common genes in PTC and HT were forecasted using the Harmonizome and miRWalk databases, respectively, and drugs targeting these genes were investigated using the Drug-Gene Interaction Database (DGIdb). The key genes in both GSE138198 and GSE33630 were further identified via Receiver Operating Characteristic (ROC) analysis. The expression of key genes was verified in external validation set and clinical samples using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). RESULTS: In total, 690 and 1945 DEGs were associated with PTC and HT, respectively; of these, 56 were shared and exhibited excellent predictive accuracy in the GSE138198 and GSE33630 cohorts. Notably, four genes, Alcohol Dehydrogenase 1B (ADH1B), Active BCR-related (ABR), alpha-1 antitrypsin (SERPINA1), and lysophosphatidic acid receptor 5 (LPAR5) were recognized as key genes shared by HT and PTC. Subsequently, EGR1 was identified as a common transcription factor regulating ABR, SERPINA1, and LPAR5 expression. These findings were confirmed using qRT-PCR and immunohistochemical analysis. CONCLUSION: Four (ADH1B, ABR, SERPINA1, and LPAR5) out of 56 common genes exhibited diagnostic potential in HT and PTC. Notably, this study, for the first time, defined the close relationship between ABR and HT/PTC progression. Overall, this study provides a basis for understanding the shared pathogenesis and underlying molecular mechanisms of HT and PTC, which might help improve patient diagnosis and prognosis.
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spelling pubmed-102662282023-06-15 Identifying and analyzing the key genes shared by papillary thyroid carcinoma and Hashimoto’s thyroiditis using bioinformatics methods Liu, Ting-ting Yin, De-tao Wang, Nan Li, Na Dong, Gang Peng, Meng-fan Front Endocrinol (Lausanne) Endocrinology BACKGROUND: Hashimoto’s thyroiditis (HT) is a chronic autoimmune disease that poses a risk factor for papillary thyroid carcinoma (PTC). The present study aimed to identify the key genes shared by HT and PTC for advancing the current understanding of their shared pathogenesis and molecular mechanisms. METHODS: HT- and PTC-related datasets (GSE138198 and GSE33630, respectively) were retrieved from the Gene Expression Omnibus (GEO) database. Genes significantly related to the PTC phenotype were identified using weighted gene co-expression network analysis (WGCNA). Differentially expressed genes (DEGs) were identified between PTC and healthy samples from GSE33630, and between HT and normal samples from GSE138198. Subsequently, functional enrichment analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Transcription factors and miRNAs regulating the common genes in PTC and HT were forecasted using the Harmonizome and miRWalk databases, respectively, and drugs targeting these genes were investigated using the Drug-Gene Interaction Database (DGIdb). The key genes in both GSE138198 and GSE33630 were further identified via Receiver Operating Characteristic (ROC) analysis. The expression of key genes was verified in external validation set and clinical samples using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). RESULTS: In total, 690 and 1945 DEGs were associated with PTC and HT, respectively; of these, 56 were shared and exhibited excellent predictive accuracy in the GSE138198 and GSE33630 cohorts. Notably, four genes, Alcohol Dehydrogenase 1B (ADH1B), Active BCR-related (ABR), alpha-1 antitrypsin (SERPINA1), and lysophosphatidic acid receptor 5 (LPAR5) were recognized as key genes shared by HT and PTC. Subsequently, EGR1 was identified as a common transcription factor regulating ABR, SERPINA1, and LPAR5 expression. These findings were confirmed using qRT-PCR and immunohistochemical analysis. CONCLUSION: Four (ADH1B, ABR, SERPINA1, and LPAR5) out of 56 common genes exhibited diagnostic potential in HT and PTC. Notably, this study, for the first time, defined the close relationship between ABR and HT/PTC progression. Overall, this study provides a basis for understanding the shared pathogenesis and underlying molecular mechanisms of HT and PTC, which might help improve patient diagnosis and prognosis. Frontiers Media S.A. 2023-05-31 /pmc/articles/PMC10266228/ /pubmed/37324256 http://dx.doi.org/10.3389/fendo.2023.1140094 Text en Copyright © 2023 Liu, Yin, Wang, Li, Dong and Peng https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Liu, Ting-ting
Yin, De-tao
Wang, Nan
Li, Na
Dong, Gang
Peng, Meng-fan
Identifying and analyzing the key genes shared by papillary thyroid carcinoma and Hashimoto’s thyroiditis using bioinformatics methods
title Identifying and analyzing the key genes shared by papillary thyroid carcinoma and Hashimoto’s thyroiditis using bioinformatics methods
title_full Identifying and analyzing the key genes shared by papillary thyroid carcinoma and Hashimoto’s thyroiditis using bioinformatics methods
title_fullStr Identifying and analyzing the key genes shared by papillary thyroid carcinoma and Hashimoto’s thyroiditis using bioinformatics methods
title_full_unstemmed Identifying and analyzing the key genes shared by papillary thyroid carcinoma and Hashimoto’s thyroiditis using bioinformatics methods
title_short Identifying and analyzing the key genes shared by papillary thyroid carcinoma and Hashimoto’s thyroiditis using bioinformatics methods
title_sort identifying and analyzing the key genes shared by papillary thyroid carcinoma and hashimoto’s thyroiditis using bioinformatics methods
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266228/
https://www.ncbi.nlm.nih.gov/pubmed/37324256
http://dx.doi.org/10.3389/fendo.2023.1140094
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