Clinical Value of Serum AREG Combined with Multimodal Ultrasound in Predicting SLN Metastasis in cN0 Stage Invasive Breast Cancer

Nana PENG; Chuchu TAO; Xiuzhi WANG; Shiying JIANG; Xiaoxi SONG

Article Contents

Article Navigation > Journal of Kunming Medical University > 2026 > Accepted Manuscript

Nana PENG, Chuchu TAO, Xiuzhi WANG, Shiying JIANG, Xiaoxi SONG. Clinical Value of Serum AREG Combined with Multimodal Ultrasound in Predicting SLN Metastasis in cN0 Stage Invasive Breast Cancer[J]. Journal of Kunming Medical University.

Citation:

PDF( 1310 KB)

Clinical Value of Serum AREG Combined with Multimodal Ultrasound in Predicting SLN Metastasis in cN0 Stage Invasive Breast Cancer

Department of Ultrasound，Xuzhou Central Hospital，Xuzhou Jiangsu 221000，China

Received Date: 2026-01-08

Abstract

Abstract

Objective To explore the predictive value of multimodal ultrasound combined with serum Amphiregulin （AREG） for sentinel lymph node （SLN） metastasis in patients with clinically negative axillary lymph node （cN0） invasive breast cancer （IBC）. Methods A total of 218 IBC patients admitted to Xuzhou Central Hospital from July 2023 to January 2025 with preoperative clinical assessment of cN0 were randomly divided into a training set （153 cases） and validation set （65 cases） in a 7:3 ratio. Based on postoperative pathology, patients were classified into SLN-positive and SLN-negative groups. Multimodal ultrasound features and serum AREG levels were compared between the two groups. The predictive value of multimodal ultrasound alone and combined with serum AREG for SLN metastasis was analyzed and validated. Results Age, menstrual status, tumor size, differentiation degree, molecular subtype, Ki-67 index, TNM stage and family history of breast cancer were comparable between the training set and the validation set （P > 0.05）. There were statistically significant differences in lymph hilum echogenicity, penetrating vessels, maximum elastic modulus （Emax）, mean elastic modulus （Esd）, peak intensity and peak time between the SLN positive group and the SLN negative group in the training set and validation set （P < 0.05）. Serum AREG levels were significantly higher in the SLN-positive group compared to the SLN-negative group in both datasets （P < 0.05）. Multivariate Logistic regression analysis showed that lymphatic echo （abnormal vs normal: OR = 3.758, 95%CI: 1.523～9.277）, perforator vessels （with vs without: OR = 3.019, 95%CI: 1.323～6.891）, Emax （every 1 kPa increase: OR = 1.046, 95%CI: 1.024～1.069）, peak intensity （every 1 dB increase: OR = 1.037, 95%CI: 1.011～1.063）, serum AREG （every 1 ng/mL increase: OR = 1.005, 95%CI: 1.001～1.009） were independent influencing factors of SLN metastasis in IBC patients （P < 0.05）. The Logit（P） predictive model based on multivariate logistic regression achieved areas under the curve （AUC） of 0.890 （95%CI: 0.848～0.954） in the training set and 0.879 （95%CI: 0.816～0.926） in the validation set. Calibration analysis demonstrated good model fit with no significant difference between predicted and observed probabilities. Decision curve analysis showed positive net clinical benefit within the threshold probability range of 10%～80% in both datasets. Conclusion Multimodal ultrasound combined with serum AREG has high predictive value for SLN metastasis in cN0-stage IBC patients, enabling more accurate preoperative prediction of SLN metastasis status and providing evidence to guide surgical decision-making.
- Invasive breast cancer,
- Serum Amphiregulin,
- Multimodal ultrasound,
- Sentinel lymph node metastasis,
- Receiver operating characteristic curve

FullText(HTML)

References(30)

References

[1]	Shi W, Su Y, Zhang R, et al. Prediction of axillary lymph node metastasis using a magnetic resonance imaging radiomics model of invasive breast cancer primary tumor[J]. Cancer Imag, 2024, 24(1): 122. doi: 10.1186/s40644-024-00771-y
[2]	王秦西, 车康明, 郭千弘. 乳腺癌中Tspan8、ITGA5表达情况与临床病理特征及预后的关系[J]. 国际检验医学杂志, 2024, 45(6): 711-715+721. doi: 10.3969/j.issn.1673-4130.2024.06.014
[3]	Park K U, Somerfield M R, Anne N, et al. Sentinel lymph node biopsy in early-stage breast cancer: ASCO guideline update[J]. J Clin Oncol, 2025, 43(14): 1720-1741. doi: 10.1200/JCO-25-00099
[4]	周桂萍, 李建柱, 焦艳丽, 等. 基于术前超声、肿瘤组织miR-328、ITGA5构建乳腺癌术后复发转移的预警模型及验证[J]. 临床误诊误治, 2025, 38(9): 37-44. doi: 10.3969/j.issn.1002-3429.2025.09.007
[5]	Kuang X, Lin L, Yuan H, et al. Association and predictive value of contrast-enhanced ultrasound features with axillary lymph node metastasis in primary breast cancer[J]. Oncol Lett, 2024, 27(3): 98. doi: 10.3892/ol.2024.14231
[6]	Huang J X, Liu F T, Sun L, et al. Comparing shear wave elastography of breast tumors and axillary nodes in the axillary assessment after neoadjuvant chemotherapy in patients with node-positive breast cancer[J]. La Radiol Med, 2024, 129(8): 1143-1155. doi: 10.1007/s11547-024-01848-1
[7]	Conticelli D, Volante M, Pietrantonio F, et al. AREG and EREG are predictive biomarkers of response to EGFR inhibition in gastroesophageal cancer[J]. Cancer Res, 2025, 85(16): 3111-3122. doi: 10.1158/0008-5472.CAN-25-0073
[8]	刘泊含, 刘鷖雯, 何怡青, 等. 血清双调蛋白、间皮素对乳腺癌辅助诊断的价值[J]. 检验医学, 2024, 39(1): 26-30. doi: 10.3969/j.issn.1673-8640.2024.01.005
[9]	国家卫生健康委员会医政医管局. 乳腺癌诊疗指南(2022年版)[J]. 中华肿瘤杂志, 2023, 45(10): 803-833. doi: 10.3969/j.issn.1005-6483.20241843
[10]	杨丽, 马强, 张春霞, 等. 超声造影体表定位联合纳米炭示踪行前哨淋巴结活检在cNO期浸润性乳腺癌病人中的应用分析[J]. 临床外科杂志, 2024, 32(5): 476-479.
[11]	He Y, Liu O, Su J, et al. Sentinel lymph node metastasis diagnosis using ultrasound plus magnetic resonance lymphangiography in breast cancer[J]. Gland Surg, 2022, 11(6): 1094-1102. doi: 10.21037/gs-22-292
[12]	Zheng B, Chen Q. Novel model based on ultrasound predict axillary lymph node metastasis in breast cancer[J]. BMC Med Imag, 2023, 23(1): 135. doi: 10.1186/s12880-023-01090-7
[13]	Wang X, Nie L, Zhu Q, et al. Artificial intelligence assisted ultrasound for the non-invasive prediction of axillary lymph node metastasis in breast cancer[J]. BMC Cancer, 2024, 24(1): 910. doi: 10.1186/s12885-024-12619-6
[14]	Li B, Zhao X, Wang Q, et al. Prediction of high nodal burden in invasive breast cancer by quantitative shear wave elastography[J]. Quant Imaging Med Surg, 2022, 12(2): 1336-1347. doi: 10.21037/qims-21-580
[15]	Eun N L, Bae S J, Youk J H, et al. Tumor-infiltrating lymphocyte level consistently correlates with lower stiffness measured by shear-wave elastography: Subtype-specific analysis of its implication in breast cancer[J]. Cancers, 2024, 16(7): 1254. doi: 10.3390/cancers16071254
[16]	Pulappadi V P, Paul S, Hari S, et al. Role of shear wave elastography as an adjunct to axillary ultrasonography in predicting nodal metastasis in breast cancer patients with suspicious nodes[J]. Br J Radiol, 2022, 95(1134): 20220055. doi: 10.1259/bjr.20220055
[17]	陈明明, 苏耀, 叶海燕, 等. 多模态超声联合超声高精细血流成像技术在乳腺癌淋巴结转移中的应用价值[J]. 中国妇幼保健, 2025, 40(5): 948-952. [知网中文带页码]
[18]	翟江, 孙小明, 杨庆华, 等. 彩色多普勒超声联合弹性成像、高精细血流成像诊断乳腺癌腋窝淋巴结转移的应用价值[J]. 河北医药, 2023, 45(22): 3437-3440.
[19]	Song Y, Liu J, Jin C, et al. Value of contrast-enhanced ultrasound combined with immune-inflammatory markers in predicting axillary lymph node metastasis of breast cancer[J]. Acad Radiol, 2024, 31(9): 3535-3545. doi: 10.1016/j.acra.2024.06.013
[20]	杨雁雯, 周伟, 李伟伟, 等. 小乳腺癌的超声造影特征与腋窝淋巴结转移的相关性研究[J]. 中国超声医学杂志, 2023, 39(8): 867-870. doi: 10.3969/j.issn.1002-0101.2023.08.010
[21]	Liu X, Wang M, Wang Q, et al. Diagnostic value of contrast-enhanced ultrasound for sentinel lymph node metastasis in breast cancer: An updated meta-analysis[J]. Breast Cancer Res Treat, 2023, 202(2): 221-231. doi: 10.1007/s10549-023-07063-2
[22]	张维, 龙松权, 唐瑞骏. 不同分子分型乳腺癌血清CYFRA21-1、HCY和CA15-3的表达差异及与术后复发、转移的关系[J]. 检验医学与临床, 2023, 20(12): 1686-1689. [机构或注册用户_知网中文带页码]
[23]	Yoon S Y, Jeong Y, Ryu J M, et al. 17β-estradiol promotes tumorigenicity through an autocrine AREG/EGFR loop in ER-α-positive breast cancer cells[J]. Cells, 2025, 14(10): 703. doi: 10.3390/cells14100703
[24]	Nakanishi T, Koma Y I, Miyako S, et al. AREG upregulation in cancer cells via direct interaction with cancer-associated fibroblasts promotes esophageal squamous cell carcinoma progression through EGFR-erk/p38 MAPK signaling[J]. Cells, 2024, 13(20): 1733. doi: 10.3390/cells13201733
[25]	Chen Y, Huo R, Kang W, et al. Tumor-associated monocytes promote mesenchymal transformation through EGFR signaling in glioma[J]. Cell Rep Med, 2023, 4(9): 101177. doi: 10.1016/j.xcrm.2023.101177
[26]	徐林生, 徐翔, 杨金凤, 等. 血清AREG水平及CT定量参数与直肠癌脉管侵犯、淋巴结转移的相关性及预测价值研究[J]. 放射学实践, 2024, 39(5): 652-657. doi: 10.13609/j.cnki.1000-0313.2024.05.015
[27]	卢梦云, 韩语诚, 胡溢洪, 等. 糖脂转运蛋白对胰腺癌PANC-1细胞增殖、迁移和侵袭的影响及其机制[J]. 吉林大学学报(医学版), 2025, 51(2): 284-295.
[28]	裴生新, 张中, 张竞, 等. 超声造影联合超声引导下穿刺活检诊断乳腺癌前哨淋巴结转移的Meta分析[J]. 临床超声医学杂志, 2022, 24(2): 93-97.
[29]	Piffkó A, Yang K, Panda A, et al. Radiation-induced amphiregulin drives tumour metastasis[J]. Nature, 2025, 643(8072): 810-819. doi: 10.1038/s41586-025-08994-0
[30]	Wei Q, Liang G, Zeng R, et al. Glucocorticoid receptor activation reprograms NK cells to drive AREG-mediated immunosuppression: A pan-cancer role for AREG[J]. Adv Sci, 2026, 13(2): e12620. doi: 10.1002/advs.202512620

Relative Articles(20)

Relative Articles

[1]	Huaran HUO, Yang YANG, Wenhui LI, Jianing DU, Zhengguo WAN. Construction and Validation of a Risk Prediction Model for Cerebral Small Vessel Disease Progression Based on Multimodal MRI Combined with Serum sRAGE. Journal of Kunming Medical University,
[2]	Quanyang LIAO, Anlv REN, Chenrong ZUO, Jv LI, Ruifen SUN, Xiaosan SU. Scutellaria barbata D.Don Water Extract Inhibits Breast Cancer Lung Metastasis by Modulating the Immune Microenvironment. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20250703
[3]	Lin WEI, Mei ZHU, Hailin ZHANG, Yuran FENG, Xi CHEN, Bailing WU, Yang YANG. Value of Binary Logit Regression Model Based on FNA-Tg and Serum Tg for Determining Lymph Node Metastasis or Recurrence of Thyroid Cancer. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20230219
[4]	Shizhou LI, Xiaoguang HE, Yan LIN, Yuxiao LI, Xi YANG, Xiaoyu WANG, Shenghao YANG. Clinical Analysis of Cervical Lymph Node Metastatic Squamous Cell Carcinoma of Unknown Primary Site. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20220710
[5]	Shifeng XIONG, Hao ZOU. Analysis of Risk Factors for Lymph Node Metastasis of Gallbladder Cancer. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20220318
[6]	Siqi XIE, Hengyu ZHANG, Hongwan LI, Mingjian TAN, Qing WANG, Sijia LI, Kai ZHENG, Dequan LIU, Shicong TANG. Correlation between Serum Valine and Methionine Levels and Clinical Features and Risk of Breast Cancer. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20220807
[7]	Wen ZHAO, Tengfei KE, Xingyue HU, Renjie ZHAO. Value of Dual-energy CT Spectrum Curve from Primary Tumor in Prediction of Central Occult Lymph Node Metastasis in Papillary Thyroid Cancer. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20221028
[8]	Hailin ZHANG, Mei ZHU, Yang YANG, Lin WEI, Xi CHEN, Bailing WU. Clinical Value of Ultrasound-guided FNA and FNA-TG in Identification of Lymph Node Metastasis of Papillary Thyroid Carcinoma. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20221220
[9]	Jianfei LU, Rui BU, Xiaoyan LIU, Xing ZHANG, Yu DING, Ran ZHANG. Efficacy of Conventional Ultrasound and Contrast-enhanced Ultrasound in Preoperative Diagnosis of Lateral Cervical Lymph Node Metastasis from Papillary Thyroid Carcinoma. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20221214
[10]	Yan SHEN, Yongfeng LI, Chunhua XIAO, Hong LI, Wei YANG, Shengning ZHANG, Yanqiong LV, Wandong YANG, Shilan. DING. Application of Multimodal Ultrasound in Post-operative Monitoring of Transplanted Livers by Donors after the Brain Death. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20220917
[11]	Wandong YANG, Yongfeng LI, Chunhua XIAO, Huimin PU, Hong LI, Wei YANG, Yan SHEN, Shilan DING, Chengcheng ZHU, Xiangfeng MIN. Clinical Application of Multimodal Ultrasound in Monitoring DBD Renal Transplantation. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20220321
[12]	Ye YUAN, Jian CHANG, Dong-bo LIU, Bao-cheng JIANG. Lymph Node Metastasis of Mixed Early Gastric Cancer and Its Influence on Prognosis. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20210321
[13]	Ya CAO, Hui ZHANG, Lin MENG, Huan-ran NI, Yi ZHAO, Guang-yan WANG, Zhi-ying LIU, Xiao-mei YANG, Li-chun YANG. Value of Color Doppler Ultrasonography, Fine Needle Aspiration Cytology, and the Level of Thyroglobulin in the Diagnosis of Cervical Lymph Node Metastasis of Papillary Thyroid Carcinoma. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20211119
[14]	Li Lei , Yang Jie , Wang Wei Lin , Wang Hu . The Correlation between the Location of Thyroid Papillary Microcarcinoma and Cervical Lymph Node Metastasis. Journal of Kunming Medical University,
[15]	Xu Rong . The Value of Detecting Paratracheal Lymph Nodes by Ultrasonography in Diagnosis of Autoimmune Thyroiditis. Journal of Kunming Medical University,
[16]	Yang Xue Jun . . Journal of Kunming Medical University,
[17]	Li Xiao Yong . . Journal of Kunming Medical University,
[18]	Dang Yong . . Journal of Kunming Medical University,
[19]	Gao He Yun . . Journal of Kunming Medical University,
[20]	Chen Yong Sheng . . Journal of Kunming Medical University,