Combination of Inflammatory Proteins in Serum Can Be Used to Diagnose Papillary Thyroid Carcinoma with Lymph Node Metastasis

Overview

Journal Discov Oncol

Publisher Springer

Date 2025 Jan 15

PMID 39812761

Authors

Yongqin Pan

Guanghao Wang

Delin Chen

Zhihui Wu

Yimwing Kei

Mingxi Xu

Affiliations

Soon will be listed here.

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.

References

Mulla M, Schulte K . Central cervical lymph node metastases in papillary thyroid cancer: a systematic review of imaging-guided and prophylactic removal of the central compartment. Clin Endocrinol (Oxf). 2011; 76(1):131-6. DOI: 10.1111/j.1365-2265.2011.04162.x. View

Neyazi M, Bharadwaj S, Bullers S, Varenyiova Z, Travis S, Arancibia-Carcamo C . Overexpression of Cancer-Associated Stem Cell Gene OLFM4 in the Colonic Epithelium of Patients With Primary Sclerosing Cholangitis. Inflamm Bowel Dis. 2021; 27(8):1316-1327. PMC: 8314119. DOI: 10.1093/ibd/izab025. View

Nozhat Z, Hedayati M . PI3K/AKT Pathway and Its Mediators in Thyroid Carcinomas. Mol Diagn Ther. 2015; 20(1):13-26. DOI: 10.1007/s40291-015-0175-y. View

Yoshihara A, Yoshimura Noh J, Watanabe N, Kunii Y, Suzuki M, Matsumoto M . Characteristics of Patients with Graves' Disease Whose Thyroid Hormone Levels Increase After Substituting Potassium Iodide for Methimazole in the First Trimester of Pregnancy. Thyroid. 2020; 30(3):451-456. DOI: 10.1089/thy.2019.0392. View

Zhang S, Yang G . IL22RA1/JAK/STAT Signaling Acts As a Cancer Target Through Pan-Cancer Analysis. Front Immunol. 2022; 13:915246. PMC: 9304570. DOI: 10.3389/fimmu.2022.915246. View

Zhang J, Ren G, Huang T, Sang Y, Zhong Y, Yi Y . miRNA-363-3p Hinders Proliferation, Migration, Invasion and Autophagy of Thyroid Cancer Cells by Controlling SYT1 Transcription to affect NF-κB. Endocr Metab Immune Disord Drug Targets. 2023; 24(1):153-162. DOI: 10.2174/1871530323666230504112553. View

Zhang W, Dang S, Zhang G, He H, Wen X . Genetic polymorphisms of IL-10, IL-18 and IL12B are associated with risk of non-small cell lung cancer in a Chinese Han population. Int Immunopharmacol. 2019; 77:105938. DOI: 10.1016/j.intimp.2019.105938. View

Zhang T, Zhang H, He L, Wang Z, Dong W, Sun W . Potential Use of 1-25-dihydroxyvitamin D in the Diagnosis and Treatment of Papillary Thyroid Cancer. Med Sci Monit. 2018; 24:1614-1623. PMC: 5872905. DOI: 10.12659/msm.909544. View

Eun N, Son E, Kim J, Gweon H, Kang J, Youk J . Comparison of the diagnostic performances of ultrasonography, CT and fine needle aspiration cytology for the prediction of lymph node metastasis in patients with lymph node dissection of papillary thyroid carcinoma: A retrospective cohort study. Int J Surg. 2018; 51:145-150. DOI: 10.1016/j.ijsu.2017.12.036. View

10.

Yu Y, Guo X, Chai J, Han Z, Ji Y, Sun J . Identification of key immune genes related to lymphatic metastasis of papillary thyroid cancer via bioinformatics analysis and experimental validation. Front Oncol. 2023; 13:1181325. PMC: 10233024. DOI: 10.3389/fonc.2023.1181325. View

11.

Omi Y, Yanagida J, Yoshida Y, Horiuchi K, Okamoto T . Risk factors for mediastinal lymph node metastasis and lung metastasis in papillary thyroid carcinoma patients: who benefits from preoperative computed tomography?. Endocr J. 2024; 71(4):357-362. DOI: 10.1507/endocrj.EJ23-0413. View

12.

Hicks H, Nassar V, Lund J, Rose M, Schweppe R . The effects of Aurora Kinase inhibition on thyroid cancer growth and sensitivity to MAPK-directed therapies. Cancer Biol Ther. 2024; 25(1):2332000. PMC: 10962586. DOI: 10.1080/15384047.2024.2332000. View

13.

Bray F, Laversanne M, Sung H, Ferlay J, Siegel R, Soerjomataram I . Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024; 74(3):229-263. DOI: 10.3322/caac.21834. View

14.

Sheng D, Ma W, Zhang R, Zhou L, Deng Q, Tu J . Ccl3 enhances docetaxel chemosensitivity in breast cancer by triggering proinflammatory macrophage polarization. J Immunother Cancer. 2022; 10(5). PMC: 9134178. DOI: 10.1136/jitc-2021-003793. View

15.

McCuaig S, Barras D, Mann E, Friedrich M, Bullers S, Janney A . The Interleukin 22 Pathway Interacts with Mutant KRAS to Promote Poor Prognosis in Colon Cancer. Clin Cancer Res. 2020; 26(16):4313-4325. DOI: 10.1158/1078-0432.CCR-19-1086. View

16.

Kim J, Gosnell J, Roman S . Geographic influences in the global rise of thyroid cancer. Nat Rev Endocrinol. 2019; 16(1):17-29. DOI: 10.1038/s41574-019-0263-x. View

17.

Krishnamohan M, Kaplanov I, Maudi-Boker S, Yousef M, Machluf-Katz N, Cohen I . Tumor Cell-Associated IL-1α Affects Breast Cancer Progression and Metastasis in Mice through Manipulation of the Tumor Immune Microenvironment. Int J Mol Sci. 2024; 25(7). PMC: 11011794. DOI: 10.3390/ijms25073950. View

18.

Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R . Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024; 4(1):47-53. PMC: 11256708. DOI: 10.1016/j.jncc.2024.01.006. View

19.

Yang Z, Wang X, Tao T, Zou J, Qiu Z, Wang L . Diagnostic value of contrast-enhanced ultrasonography in the preoperative evaluation of lymph node metastasis in papillary thyroid carcinoma: a single-center retrospective study. BMC Surg. 2023; 23(1):325. PMC: 10599078. DOI: 10.1186/s12893-023-02199-w. View

20.

Bo J, Mao S, Yang J, Wang L, Zheng J, Zhang C . Rhodiolin inhibits the PI3K/AKT/mTOR signaling pathway via the glycolytic enzyme GPI in human papillary thyroid cancer. Phytomedicine. 2024; 132:155804. DOI: 10.1016/j.phymed.2024.155804. View