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pmid:37324256
Identifying and analyzing the key genes shared by papillary thyroid carcinoma and Hashimoto's thyroiditis using bioinformatics methods.
Ting-Ting Liu · De-Tao Yin · Nan Wang · Na Li · Gang Dong · Meng-Fan Peng
Frontiers in endocrinology · 2023 doi:10.3389/fendo.2023.1140094
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Complete file
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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.\nMethods: 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).\nResults: 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.\nConclusion: 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.", "claims": [{"id": "claim-method", "statement": "Furthermore, according to the gene expression patterns, the common genes were included in subsequent Receiver Operating Characteristic (ROC) analyses for identifying their predictive accuracy in GSE33630 (PTC vs Normal) and GSE138198 (HT vs Normal) datasets using the ‘pROC’ package, where the best threshold value was selected according to the Youden index.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37324256", "locator": "sections[6] \"Recognition of common key genes in HT and PTC\" paragraph 2", "quote": "Furthermore, according to the gene expression patterns, the common genes were included in subsequent Receiver Operating Characteristic (ROC) analyses for identifying their predictive accuracy in GSE33630 (PTC vs Normal) and GSE138198 (HT vs Normal) datasets using the ‘pROC’ package, where the best threshold value was selected according to the Youden index."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material ."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Four of 56 common genes—ADH1B, ABR, SERPINA1, and LPAR5—exhibited diagnostic potential in Hashimoto’s thyroiditis and papillary thyroid carcinoma.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37324256", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Four (ADH1B, ABR, SERPINA1, and LPAR5) out of 56 common genes exhibited diagnostic potential in HT and PTC."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Four of 56 common genes—ADH1B, ABR, SERPINA1, and LPAR5—exhibited diagnostic potential in Hashimoto’s thyroiditis and papillary thyroid carcinoma.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37324256"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE138198"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE138198"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37324256", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fendo.2023.1140094", "sha256": "sha256:46c421f19d2e3736cfc260478707493207b53497be13e111cc5cc3d53968f9a2", "bytes": 67303, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fendo.2023.1140094", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10266228", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE138198", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138198", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE138198", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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Results: In total, 690 and 1945 DEGs", "se findings were confirmed using qRT-PCR and immunohistochemical analysis. Conclusion: Four (ADH1B, ABR, SERP", "reaction (qRT-PCR) and immunohistochemistry (IHC). Results: In total, 690 and 1945 DEGs were", "ce in papillary thyroid carcinoma (PTC). (A) Immunohistochemical (IHC) analysis of ABR, ADH1B, LPAR5, and SER"], "order_basis": "paper_text_order:1478", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["date these expression patterns, we performed RT-qPCR on tumor tissues and NAT collected from nine", "e these expression patterns, we performed RT-qPCR on tumor tissues and NAT collected from nine"], "order_basis": "paper_text_order:4045", "id": "assay:2"}, {"role": "data_generation", "definition_id": "clinical_cohort", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["on tumor tissues and NAT collected from nine patients with PTC in HT. Consistent with the bioinformatic", "n tumor tissues and NAT collected from eight patients with PTC in HT using IHC. In agreement with the b"], "order_basis": "paper_text_order:4098", "id": "assay:3"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Wilcoxon"], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}