Research advances in contrast-enhanced ultrasound characteristics of vascular heterogeneity and its molecular mechanisms in papillary thyroid cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

SUN Xu ¹ , WU Jiahuan ² , LIU Xiatong ¹ ,  WANG Fanbo ²

1. Jiamusi University, Jiamusi, Heilongjiang 154007, P. R. China;
2. The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154003, P. R. China;

Corresponding?author：

WANG Fanbo, Email: wfanbo@jmsu.edu.cn

Keywords：

papillary thyroid cancer; contrast-enhanced ultrasound; vascular heterogeneity; prognosis; molecular mechanism

DOI：

10.7507/1007-9424.202510044

Video：

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Objective To elucidate the evaluation of vascular heterogeneity in papillary thyroid cancer (PTC) by contrast-enhanced ultrasound (CEUS) and its relationship with key prognostic indicators of PTC, aiming to provide theoretical support for precise preoperative assessment and individualized treatment of PTC. Method The recent advances in domestic and international research on the application of CEUS for evaluating vascular heterogeneity in PTC and its association with prognosis were reviewed. Results CEUS can effectively assess the vascular heterogeneity of PTC through microbubble contrast technology. Among the features, hypervascular characteristics (hyper- or iso-enhancement) are independently associated with gross extrathyroidal extension, clinically node-positive status, and structural recurrence, while hypovascular characteristics (hypo-enhancement) suggest a lower risk of invasiveness. Studies on molecular mechanisms indicate that the core drivers of vascular heterogeneity in PTC are the differential activation of metabolic pathways (such as oxidative phosphorylation and Hippo signaling pathway), rather than classical angiogenesis pathways (e.g., vascular endothelial growth factor). Furthermore, long noncoding RNAs may indirectly participate in this process by regulating metabolism-related genes. Conclusions As a non-invasive preoperative imaging tool, CEUS can effectively evaluate the vascular heterogeneity of PTC and hold marked potential in predicting PTC prognosis. In the future, through multicenter validation, technical optimization, and further mechanistic research, CEUS has the potential to be integrated into the precision diagnosis and treatment system for PTC, providing a critical basis for prognosis risk stratification and individualized interventions based on vascular characteristics.

Citation： SUN Xu, WU Jiahuan, LIU Xiatong, WANG Fanbo. Research advances in contrast-enhanced ultrasound characteristics of vascular heterogeneity and its molecular mechanisms in papillary thyroid cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2026, 33(3): 398-405. doi: 10.7507/1007-9424.202510044 Copy

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1. 袁雙龍, 薛江, 牛小葉. 基因變異與乳頭狀甲狀腺癌診斷、治療及預后關系: 文獻綜述. 中國普外基礎與臨床雜志, 2024, 31(10): 1272-1280.
2. Shi XQ, Liu XT, Liu XH, et al. Phosphoglycerate kinase 1 as a potential prognostic biomarker in papillary thyroid carcinoma. Front Pharmacol, 2025, 16: 1542159. doi: 10.3389/fphar.2025.1542159.
3. 劉飛, 秦貴軍, 許莉軍, 等. 甲狀腺乳頭狀癌患者術后促甲狀腺素水平與骨代謝指標及骨密度的關系. 癌癥進展, 2025, 23(13): 1501-1504.
4. 毛安寧. 中央區淋巴結轉移數目及比例對甲狀腺乳頭狀癌預后分析. 南昌: 南昌大學, 2025.
5. Li X, Zhuang M, Hu Z, et al. Comparison of micro-flow imaging and contrast-enhanced ultrasound in monitoring microwave ablation of papillary thyroid carcinoma: efficacy, safety, and cost-effectiveness. Front Oncol, 2025, 15: 1545509. doi: 10.3389/fonc.2025.1545509.
6. 陸嬋. 甲狀腺乳頭狀癌超聲造影特征與腫瘤大小、頸部淋巴結轉移的關系研究. 百色: 右江民族醫學院, 2024.
7. 張美秀, 黃志新, 張穎, 等. 甲狀腺乳頭狀癌患者術前MACIS評分對預后的預測效果分析. 腫瘤綜合治療電子雜志, 2025, 11(2): 113-117.
8. Zhan J, Zhang LH, Yu Q, et al. Prediction of cervical lymph node metastasis with contrast-enhanced ultrasound and association between presence of BRAF^V600E and extrathyroidal extension in papillary thyroid carcinoma. Ther Adv Med Oncol, 2020, 12: 1758835920942367. doi: 10.1177/1758835920942367.
9. 劉艷, 利青, 黃柯, 等. 超聲造影及相關新技術在甲狀腺乳頭狀癌診療中的研究進展. 分子影像學雜志, 2025, 48(7): 917-921.
10. 馮子恩. 單側甲狀腺乳頭狀癌對側頸部中央區淋巴結轉移危險因素臨床研究. 贛州: 贛南醫科大學, 2025.
11. 樊金芳, 周偉, 王龔. 基于超聲特征構建列線圖預測峽部甲狀腺乳頭狀癌頸部淋巴結轉移. 中國醫學計算機成像雜志, 2025, 31(2): 270-276.
12. Tabiti H, Guensi A, Bendahhou K. Epidemiological and histological characteristics of differentiated thyroid carcinoma: a case of the Department of Nuclear Medicine at Ibn Rochd Hospital, Casablanca, Morocco. Cureus, 2024, 16(1): e52033. doi: 10.7759/cureus.52033.
13. 張茜. 超聲影像組學輔助甲狀腺癌診斷、分型及淋巴結轉移預測的研究. 沈陽: 中國醫科大學, 2024.
14. 劉琦. 超聲造影在不同大小甲狀腺良惡性結節鑒別診斷中的價值. 宜昌: 三峽大學, 2024.
15. 樊小虎, 于衛華, 江宣陵. 超聲造影聯合血清DKK-1、Gal-1對分化型甲狀腺腫瘤的診斷價值及其與TNM分期、腫瘤惡性程度相關性分析. 臨床和實驗醫學雜志, 2023, 22(7): 757-762.
16. Skuletic V, Radosavljevic GD, Pantic J, et al. Angiogenic and lymphangiogenic profiles in histological variants of papillary thyroid carcinoma. Pol Arch Intern Med, 2017, 127(6): 429-437.
17. Perivoliotis K, Samara AA, Koutoukoglou P, et al. Microvessel density in differentiated thyroid carcinoma: a systematic review and meta-analysis. World J Methodol, 2022, 12(5): 448-458.
18. 劉睿. 甲狀腺乳頭狀癌淋巴轉移相關基因預后模型的建立及機制探索. 北京: 北京協和醫學院, 2022.
19. Yu Q, Hao W, He Y, et al. Multi-omics analysis unveils dysregulation of the tumor immune microenvironment and development of a machine learning-based multi-gene classifier for predicting lateral lymph node metastasis in papillary thyroid carcinoma. Endocrine, 2025, 90(1): 1-16.
20. 馮千清. 超聲造影到達時間參數成像鑒別甲狀腺結節良惡性的價值研究. 沈陽: 中國醫科大學, 2024.
21. 丁姣姣, 莊曉晨, 茍政江, 等. 超聲造影在具有可疑特征的甲狀腺良性結節中的鑒別診斷價值. 醫學影像學雜志, 2025, 35(3): 31-35.
22. Zhang Y, Zhang X, Li J, et al. Contrast-enhanced ultrasound: a valuable modality for extracapsular extension assessment in papillary thyroid cancer. Eur Radiol, 2021, 31(7): 4568-4575.
23. ?y?ka A, Dobruch-Sobczak K, Piotrzkowska-Wróblewska H, et al. The utility of contrast-enhanced ultrasound (CEUS) in assessing the risk of malignancy in thyroid nodules. Cancers (Basel), 2024, 16(10): 1911. doi: 10.3390/cancers16101911.
24. 周易, 梁蕾, 孟曉暄, 等. 實時CEUS評估甲狀腺乳頭狀癌侵襲性及其與病理微血管密度的關系. 中國醫學影像技術, 2019, 35(7): 993-996.
25. Yang S, Huang C, Zhou J, et al. The relationship between the extent of extrathyroidal extension and lymph node metastasis based on propensity score matching analysis. Gland Surg, 2025, 14(11): 2258-2270.
26. Ito Y, Tomoda C, Uruno T, et al. Prognostic significance of extrathyroid extension of papillary thyroid carcinoma: massive but not minimal extension affects the relapse-free survival. World J Surg, 2006, 30(5): 780-786.
27. 李文, 羅渝昆, 龍梅. 超聲造影顯示的血供在甲狀腺乳頭狀癌預后預測中的研究進展. 醫學影像學雜志, 2025, 35(3): 126-130.
28. Li W, Qiu S, Ren L, et al. Ultrasound and contrast-enhanced ultrasound characteristics associated with cN1 and microscopic pN1 in papillary thyroid carcinoma. Front Endocrinol (Lausanne), 2022, 12: 810630. doi: 10.3389/fendo.2021.810630.
29. Wang Y, Nie F, Wang G, et al. Value of combining clinical factors, conventional ultrasound, and contrast-enhanced ultrasound features in preoperative prediction of central lymph node metastases of different sized papillary thyroid carcinomas. Cancer Manag Res, 2021, 13: 3403-3415.
30. Wijewardene A, Hoang J, Maw AM, et al. I-PET score: combining whole body iodine and ¹⁸F-FDG PET/CT imaging to predict progression in structurally or biochemically incomplete thyroid cancer. Clin Endocrinol (Oxf), 2023, 98(3): 436-446.
31. Tasoulas J, Tsourouflis G, Theocharis S. Neovascularization: an attractive but tricky target in thyroid cancer. Expert Opin Ther Targets, 2018, 22(9): 799-810.
32. Liu Y, Liu H, Qian CL, et al. Utility of quantitative contrast-enhanced ultrasound for the prediction of extracapsular extension in papillary thyroid carcinoma. Sci Rep, 2017, 7(1): 1472. doi: 10.1038/s41598-017-01650-2.
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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research advances in contrast-enhanced ultrasound characteristics of vascular heterogeneity and its molecular mechanisms in papillary thyroid cancer

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