Advances in Laboratory Diagnosis of Lymph Node Metastasis in Papillary Thyroid Carcinoma: From Diagnostic Biomarkers to Multimodal Combined Applications
Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v6i4.4810
Abstract
Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the head and neck, with a generally slow disease progression and favorable prognosis in most patients. However, lymph node metastasis in a small subset of patients can reduce the five-year disease-free survival rate from 94.8% to 73.1%. Studies have confirmed that lymph node metastasis is a risk factor for poor prognosis. Therefore, this article analyzes and compares the diagnostic value of biomarkers, liquid biopsy, and combined detection techniques to evaluate their diagnostic efficacy in lymph node metastasis and prognosis, aiming to provide evidence-based support for optimizing clinical diagnostic pathways.
Keywords
papillary thyroid carcinoma; lymph node metastasis; laboratory diagnosis; serological markers; molecular biological testing
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[25] TALI G, PAYNE A E, HUDSON T J, et al. The Difference in Clinical Behavior of Gene Fusions Involving RET/PTC Fusions and THADA/IGF2BP3 Fusions in Thyroid Nodules[J]. Cancers (Basel), 2023, 15(13).
[26]Yu L, Wu X P, Gai J F, et al. The application value of ultrasound combined with FNA Tg in cervical lymph node metastasis of papillary thyroid carcinoma. Chinese Journal of Ultrasound in Medicine[J], 2023, 39(03):245-247.
[27] Ni P, Yan Z L, Zhang S Y, et al. Analysis of the diagnostic value of fine needle aspiration cytology combined with biopsy fluid thyroglobulin and BRAFV600E/RET fusion gene detection for cervical lymph node metastasis in papillary thyroid carcinoma. China Medical Herald[J], 2025, 22(09):97-101.
[28] TIAN D, LI X, JIA Z. Analysis of Risk Factors and Risk Prediction for Cervical Lymph Node Metastasis in Thyroid Papillary Carcinoma[J]. Cancer Manag Res, 2024, 16:1571-1585.
[29] NIKANJAM M, KATO S, KURZROCK R. Liquid biopsy: current technology and clinical applications[J]. J Hematol Oncol, 2022, 15(1):131.
[30] IYER P C, COTE G J, HAI T, et al. Circulating BRAF V600E Cell-Free DNA as a Biomarker in the Management of Anaplastic Thyroid Carcinoma[J]. JCO Precis Oncol, 2018, 2.
[31] QIN Y, WANG J R, WANG Y, et al. Clinical Utility of Circulating Cell-Free DNA Mutations in Anaplastic Thyroid Carcinoma[J]. Thyroid, 2021, 31(8):1235-1243.
[32] CASTAGNA M G, MARZOCCHI C, PILLI T, et al. MicroRNA expression profile of thyroid nodules in fine-needle aspiration cytology: a confirmatory series[J]. J Endocrinol Invest, 2019, 42(1):97-100.
[33] Liu X L, Chen X X, Chen L, et al. Prediction factors of cervical lymph node metastasis in papillary thyroid carcinoma by ultrasound and BRAFV600E gene. Guangdong Medical Journal[J], 2022, 43(04):457-461.
[34] Shen Z Q. The predictive value of thyroid globulin and its antibody detection combined with CT enhancement for cervical lymph node metastasis in papillary thyroid carcinoma. Image Technology[J], 2025, 37(02):45-48.
[35] Wang Y. Prediction of lymph node metastasis with a short diameter less than 8mm in the neck of papillary thyroid carcinoma based on radiomics [D]. China Medical University, 2024.
[36] Guan P, Huang W J, Zhao Y Y, et al. constructed a column chart based on conventional ultrasound combined with ultra micro vascular imaging to predict the value of central lymph node metastasis in papillary thyroid cancer. Chinese Computed Medical Imaging[J], 2025, 31(02):263-269.
[37] YU J, DENG Y, LIU T, et al. Lymph node metastasis prediction of papillary thyroid carcinoma based on transfer learning radiomics[J]. Nat Commun, 2020, 11(1):4807.
[2] JIANG H J, HSIAO P J. Clinical application of the ultrasound-guided fine needle aspiration for thyroglobulin measurement to diagnose lymph node metastasis from differentiated thyroid carcinoma-literature review[J]. Kaohsiung J Med Sci, 2020, 36(4):236-243.
[3] PACINI F, CASTAGNA M G, BRILLI L, et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2012, 23 Suppl 7:vii110-9.
[4] Liu X Y, Zhao H J, Xing H, et al. The Diagnostic Value of Serum Exosomal miRNA Expression at Different Iodine Levels for Early Detection of Lymph Node Metastasis in Papillary Thyroid Carcinoma. Journal of Modern Oncology[J], 2023, 31(16):3014-3018.
[5] SUN Z, SHI K, YANG S, et al. Effect of exosomal miRNA on cancer biology and clinical applications[J]. Mol Cancer, 2018, 17(1):147.
[6] DAI D, TAN Y, GUO L, et al. Identification of exosomal miRNA biomarkers for diagnosis of papillary thyroid cancer by small RNA sequencing[J], 2020, 182(1):111-121.
[7] CAPRIGLIONE F, VERRIENTI A, CELANO M, et al. Analysis of serum microRNA in exosomal vehicles of papillary thyroid cancer[J]. Endocrine, 2022, 75(1):185-193.
[8] CELAKOVSKY P, KOVARIKOVA H, CHROBOK V, et al. MicroRNA Deregulation in Papillary Thyroid Cancer and its Relationship With BRAF V600E Mutation[J]. In Vivo, 2021, 35(1):319-323.
[9] Lou Y Q, Chen H Y, Yang M M, et al. Abnormal expression and research progress of microRNAs in papillary thyroid carcinoma. Smart Healthcare[J], 2021, 7(22):37-38+41.
[10] Qin X J, Xue G, Wu J F. The role and research status of microRNAs in papillary thyroid carcinoma. Chinese Journal of Otorhinolaryngology-Skull Base Surgery[J], 2020, 26(03):349-354.
[11] YORUKER E E, TERZIOGLU D, TEKSOZ S, et al. MicroRNA Expression Profiles in Papillary Thyroid Carcinoma, Benign Thyroid Nodules and Healthy Controls[J]. J Cancer, 2016, 7(7):803-9.
[12] WEI Z L, GAO A B, WANG Q, et al. MicroRNA-221 promotes papillary thyroid carcinoma cell migration and invasion via targeting RECK and regulating epithelial-mesenchymal transition[J]. Onco Targets Ther, 2019, 12:2323-2333.
[13] XIANG D, TIAN B, YANG T, et al. miR-222 expression is correlated with the ATA risk stratifications in papillary thyroid carcinomas[J]. Medicine (Baltimore), 2019, 98(25):e16050.
[14] PAMEDYTYTE D, SIMANAVICIENE V, DAUKSIENE D, et al. SAT-LB096 relationship between MicroRNA expression levels and clinicopathological parameters and recurrence of papillary thyroid carcinoma[J], 2019, 3(Supplement_1):SAT-LB096.
[15] ROGUCKI M, BUCZYŃSKA A, KRĘTOWSKI A J, et al. The Importance of miRNA in the Diagnosis and Prognosis of Papillary Thyroid Cancer[J]. J Clin Med, 2021, 10(20).
[16] YU H W, PARK E, LEE J K, et al. Analyzing circulating tumor cells and epithelial-mesenchymal transition status of papillary thyroid carcinoma patients following thyroidectomy: a prospective cohort study[J]. Int J Surg, 2024, 110(6):3357-3364.
[17] YU M, DENG J, GU Y, et al. Preoperative High Level of Circulating Tumor Cells is an Independent Risk Factor for Central Lymph Node Metastasis in Papillary Thyroid Carcinoma with Maximum Lesion Diameter ≤1.0 cm[J]. Int J Gen Med, 2024, 17:4907-4916.
[18] Jia H Z, Zhang B L, Zhang J, et al. Study on the mechanism of hsa_circRNA-0073762 promoting invasion, metastasis, and proliferation of papillary thyroid carcinoma cells. Journal of Hebei Medical University[J], 2025, 46(04):444-452.
[19] XING M. Prognostic utility of BRAF mutation in papillary thyroid cancer[J]. Mol Cell Endocrinol, 2010, 321(1):86-93.
[20] CHEN Y, SADOW P M, SUH H, et al. BRAF(V600E) Is Correlated with Recurrence of Papillary Thyroid Microcarcinoma: A Systematic Review, Multi-Institutional Primary Data Analysis, and Meta-Analysis[J]. Thyroid, 2016, 26(2):248-55.
[21] SUDOKO C K, JENKS C M, BAUER A J, et al. Thyroid Lobectomy for T1 Papillary Thyroid Carcinoma in Pediatric Patients[J]. JAMA Otolaryngol Head Neck Surg, 2021, 147(11):943-950.
[22] ZHANG Z, ZHANG X, YIN Y, et al. Integrating BRAF(V600E) mutation, ultrasonic and clinicopathologic characteristics for predicting the risk of cervical central lymph node metastasis in papillary thyroid carcinoma[J]. BMC Cancer, 2022, 22(1):461.
[23] RICCIO I, LAFORTEZA A, LANDAU M B, et al. Decoding RAS mutations in thyroid cancer: A meta-analysis unveils specific links to distant metastasis and increased mortality[J]. Am J Otolaryngol, 2025, 46(1):104570.
[24] KHAN M S, QADRI Q, MAKHDOOMI M J, et al. RET/PTC Gene Rearrangements in Thyroid Carcinogenesis: Assessment and Clinico-Pathological Correlations[J]. Pathol Oncol Res, 2020, 26(1):507-513.
[25] TALI G, PAYNE A E, HUDSON T J, et al. The Difference in Clinical Behavior of Gene Fusions Involving RET/PTC Fusions and THADA/IGF2BP3 Fusions in Thyroid Nodules[J]. Cancers (Basel), 2023, 15(13).
[26]Yu L, Wu X P, Gai J F, et al. The application value of ultrasound combined with FNA Tg in cervical lymph node metastasis of papillary thyroid carcinoma. Chinese Journal of Ultrasound in Medicine[J], 2023, 39(03):245-247.
[27] Ni P, Yan Z L, Zhang S Y, et al. Analysis of the diagnostic value of fine needle aspiration cytology combined with biopsy fluid thyroglobulin and BRAFV600E/RET fusion gene detection for cervical lymph node metastasis in papillary thyroid carcinoma. China Medical Herald[J], 2025, 22(09):97-101.
[28] TIAN D, LI X, JIA Z. Analysis of Risk Factors and Risk Prediction for Cervical Lymph Node Metastasis in Thyroid Papillary Carcinoma[J]. Cancer Manag Res, 2024, 16:1571-1585.
[29] NIKANJAM M, KATO S, KURZROCK R. Liquid biopsy: current technology and clinical applications[J]. J Hematol Oncol, 2022, 15(1):131.
[30] IYER P C, COTE G J, HAI T, et al. Circulating BRAF V600E Cell-Free DNA as a Biomarker in the Management of Anaplastic Thyroid Carcinoma[J]. JCO Precis Oncol, 2018, 2.
[31] QIN Y, WANG J R, WANG Y, et al. Clinical Utility of Circulating Cell-Free DNA Mutations in Anaplastic Thyroid Carcinoma[J]. Thyroid, 2021, 31(8):1235-1243.
[32] CASTAGNA M G, MARZOCCHI C, PILLI T, et al. MicroRNA expression profile of thyroid nodules in fine-needle aspiration cytology: a confirmatory series[J]. J Endocrinol Invest, 2019, 42(1):97-100.
[33] Liu X L, Chen X X, Chen L, et al. Prediction factors of cervical lymph node metastasis in papillary thyroid carcinoma by ultrasound and BRAFV600E gene. Guangdong Medical Journal[J], 2022, 43(04):457-461.
[34] Shen Z Q. The predictive value of thyroid globulin and its antibody detection combined with CT enhancement for cervical lymph node metastasis in papillary thyroid carcinoma. Image Technology[J], 2025, 37(02):45-48.
[35] Wang Y. Prediction of lymph node metastasis with a short diameter less than 8mm in the neck of papillary thyroid carcinoma based on radiomics [D]. China Medical University, 2024.
[36] Guan P, Huang W J, Zhao Y Y, et al. constructed a column chart based on conventional ultrasound combined with ultra micro vascular imaging to predict the value of central lymph node metastasis in papillary thyroid cancer. Chinese Computed Medical Imaging[J], 2025, 31(02):263-269.
[37] YU J, DENG Y, LIU T, et al. Lymph node metastasis prediction of papillary thyroid carcinoma based on transfer learning radiomics[J]. Nat Commun, 2020, 11(1):4807.
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