Combination of inflammatory proteins in serum can be used to diagnose papillary thyroid carcinoma with lymph node metastasis

Abstract Background Accurately distinguishing lymph node metastases (LNM) from papillary thyroid carcinomas (PTC) is crucial in clinical practice. The role of the immune system in PTC-LNM has attracted increasing attention. The aim of the present study was to evaluate the differential expression of...

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Main Authors: Yongqin Pan, Guanghao Wang, Delin Chen, Zhihui Wu, Yimwing Kei, Mingxi Xu
Format: Article
Language:English
Published: Springer 2025-01-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-01793-z
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author Yongqin Pan
Guanghao Wang
Delin Chen
Zhihui Wu
Yimwing Kei
Mingxi Xu
author_facet Yongqin Pan
Guanghao Wang
Delin Chen
Zhihui Wu
Yimwing Kei
Mingxi Xu
author_sort Yongqin Pan
collection DOAJ
description Abstract Background Accurately distinguishing lymph node metastases (LNM) from papillary thyroid carcinomas (PTC) is crucial in clinical practice. The role of the immune system in PTC-LNM has attracted increasing attention. The aim of the present study was to evaluate the differential expression of 92 immune-related proteins in the serum and identify their potential diagnostic effects in patients with PTC-LNM. Methods The 92 immune-related proteins were analyzed using a proximity extension assay. In addition, logistic regression and least absolute shrinkage and selection operator regression methods were used to develop combined diagnostic markers for thyroid cancer. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic validity. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis were used to analyze the potential regulatory pathways. Results Five proteins, including IL-22RA1, IL-12B, CCL4, CCL3, and IL-1α, were significantly elevated in the serum of patients with LNM. The combined diagnosis of these five proteins demonstrated excellent diagnostic performance in distinguishing patients with PTC-LNM (area under the curve = 0.967, sensitivity = 0.941, and specificity = 0.889). Further analysis revealed that IL12B and IL1A mRNAs were significantly overexpressed in patients with PTC-LNM. This study also showed that the IL12B and IL1A was closely related to the PI3K-AKT, NF-κB, and MAPK signaling pathways. Conclusion The combination of IL-22RA1, IL-12B, CCL4, CCL3, and IL-1α represents a promising diagnostic panel for PTC-LNM. These findings provide a novel set of diagnostic markers for PTC-LNM based on serum inflammatory protein levels.
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spelling doaj-art-84e79dd2eb42427ba1be04e3accf59d12025-01-19T12:29:17ZengSpringerDiscover Oncology2730-60112025-01-0116111210.1007/s12672-025-01793-zCombination of inflammatory proteins in serum can be used to diagnose papillary thyroid carcinoma with lymph node metastasisYongqin Pan0Guanghao Wang1Delin Chen2Zhihui Wu3Yimwing Kei4Mingxi Xu5Department of Thyroid Surgery, The First Affiliated Hospital of Jinan UniversityDepartment of Thyroid Surgery, The First Affiliated Hospital of Jinan UniversityDepartment of Thyroid Surgery, The First Affiliated Hospital of Jinan UniversityDepartment of Thyroid Surgery, The First Affiliated Hospital of Jinan UniversityDepartment of Thyroid Surgery, The First Affiliated Hospital of Jinan UniversityDepartment of Thyroid Surgery, The First Affiliated Hospital of Jinan UniversityAbstract Background Accurately distinguishing lymph node metastases (LNM) from papillary thyroid carcinomas (PTC) is crucial in clinical practice. The role of the immune system in PTC-LNM has attracted increasing attention. The aim of the present study was to evaluate the differential expression of 92 immune-related proteins in the serum and identify their potential diagnostic effects in patients with PTC-LNM. Methods The 92 immune-related proteins were analyzed using a proximity extension assay. In addition, logistic regression and least absolute shrinkage and selection operator regression methods were used to develop combined diagnostic markers for thyroid cancer. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic validity. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis were used to analyze the potential regulatory pathways. Results Five proteins, including IL-22RA1, IL-12B, CCL4, CCL3, and IL-1α, were significantly elevated in the serum of patients with LNM. The combined diagnosis of these five proteins demonstrated excellent diagnostic performance in distinguishing patients with PTC-LNM (area under the curve = 0.967, sensitivity = 0.941, and specificity = 0.889). Further analysis revealed that IL12B and IL1A mRNAs were significantly overexpressed in patients with PTC-LNM. This study also showed that the IL12B and IL1A was closely related to the PI3K-AKT, NF-κB, and MAPK signaling pathways. Conclusion The combination of IL-22RA1, IL-12B, CCL4, CCL3, and IL-1α represents a promising diagnostic panel for PTC-LNM. These findings provide a novel set of diagnostic markers for PTC-LNM based on serum inflammatory protein levels.https://doi.org/10.1007/s12672-025-01793-zProximity extension assayBiomarkerLymph node metastasisPapillary thyroid carcinoma
spellingShingle Yongqin Pan
Guanghao Wang
Delin Chen
Zhihui Wu
Yimwing Kei
Mingxi Xu
Combination of inflammatory proteins in serum can be used to diagnose papillary thyroid carcinoma with lymph node metastasis
Discover Oncology
Proximity extension assay
Biomarker
Lymph node metastasis
Papillary thyroid carcinoma
title Combination of inflammatory proteins in serum can be used to diagnose papillary thyroid carcinoma with lymph node metastasis
title_full Combination of inflammatory proteins in serum can be used to diagnose papillary thyroid carcinoma with lymph node metastasis
title_fullStr Combination of inflammatory proteins in serum can be used to diagnose papillary thyroid carcinoma with lymph node metastasis
title_full_unstemmed Combination of inflammatory proteins in serum can be used to diagnose papillary thyroid carcinoma with lymph node metastasis
title_short Combination of inflammatory proteins in serum can be used to diagnose papillary thyroid carcinoma with lymph node metastasis
title_sort combination of inflammatory proteins in serum can be used to diagnose papillary thyroid carcinoma with lymph node metastasis
topic Proximity extension assay
Biomarker
Lymph node metastasis
Papillary thyroid carcinoma
url https://doi.org/10.1007/s12672-025-01793-z
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