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This study developed a noninvasive serological assay to predict RAIT efficacy by measuring 141 inflammatory/immune-related proteins and lymphocyte subsets in 28 PTC patients before treatment and at 30 and 90 days after RAIT. Patients were classified into excellent response (ER) and nonexcellent response (NER); higher pre-RAIT HGF levels in NER predicted disease-free survival. 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\nMultiplex Immune Profiling Reveals the Role of Serum Immune Proteomics in Predicting Response to Radioiodine after Total Resection of Papillary Thyroid Carcinoma  \nWanshu Peng,† Shujing Li,† Jiaxin Cao, Weiming Zhang, Peifen Chen, Juan Guo, Jin Zhang, Suyun Yang, Lixiang Wu, Yanjie Li, Bo Yu, Yubo Zhang, Ke Yang, Yuanzheng Ding, Chunfang Zan, Jing Jia, Junping Lv, Xinyu Zhang, Zhifang Wu, Jing Liu, * Sijin Li, * and Haiyan Liu*  \n Cite This: J. Proteome Res. 2026, 25, 418−436  \nRead Online  \n\n|  |  |  |  |  |  |\n| --- | --- | --- | --- | --- | --- |\n| ACCESS   | Metrics & More |  |  Article Recommendations |  | *sı Supporting Information |\n\nABSTRACT: Radioactive iodine therapy (RAIT) is a common postsurgery treatment for papillary thyroid carcinoma (PTC), but some patients respond poorly. This study aimed to develop a noninvasive serological assay to predict RAIT efficacy. We examined levels of 141 inflammatory/immune-related proteins and lymphocyte subsets in 28 PTC patients before, at 30 days, and at 90 days after RAIT. Patients were categorized into excellent response (ER) and nonexcellent response (NER) groups. Pre-RAIT HGF levels were significantly higher in the NER group and predicted a disease-free survival in an independent cohort. Bioinformatics analysis revealed a strong correlation between high HGF expression and immune cell infiltration in the tumor microenvironment. This study proposes a pre-RAIT serum protein (PSP) panel comprising FASLG, CXCL12, and HGF for risk stratification, with higher scores indicating a poorer prognosis, although this requires validation in larger cohorts. It underscores the importance of dynamic immune monitoring and proposes a novel, noninvasive strategy that leverages the role of systemic immunity for clinical patient stratification and outcome prediction.  \nKEYWORDS: radioactive iodine therapy, papillary thyroid carcinoma, serum immune proteomics, predictive model, efficacy assessment  \n■ INTRODUCTION  \nAccording to the GLOBOCAN 2020 database, thyroid cancer (TC) is the ninth most common cancer and the most prevalent endocrine malignancy globally.1 The majority of TC cases are papillary thyroid carcinomas (PTC), constituting over 85% of all cases.2  \nStandard treatments for PTC include thyroidectomy and radioactive iodine therapy (RAIT).3 However, the response to RAIT varies among patients. Distinct responses to RAIT determine different subsequent clinical strategies and prognosis. The 2025 American Thyroid Association guidelines recommend close follow-up for high-risk PTC patients after RAIT.4 Serum biomarkers and imaging data collected 6−12 months post-RAIT categorize patients into excellent response (ER) and nonexcellent response (NER) groups. The ER group includes those with negative imaging and thyroglobulin antibody (TgAb), low thyroglobulin (Tg) levels (≤0.2 ng/mL), or thyroid-stimulating hormone (TSH) stimulated Tg (sTg) (\u003C1 ng/mL). NER includes those not meeting these criteria. Studies show that about 60% of patients with aggressive metastatic differentiated thyroid carcinoma (DTC) become resistant to RAI, leading to poor outcomes.5 Hence, the need for a reliable tool predicting  \n© 2025 The Authors. Published by American Chemical Society  \ntherapeutic response pre-RAIT is vital and urgent but has not been fulfilled yet.  \nRecent research indicates that changes in the tumor microenvironment (TME) immune landscape are tied to disease progression in PTC, with an increase in protumor immune cells and a decrease in antitumor cells as the disease advances. These findings indicate that PTC tumors may enhance their immunosuppressive abilities by recruiting immunoregulatory cells to evade host immune defenses.6,7 A recent study showed that LAMP3+ dendritic cells interacting with T cell subsets promote immune escape in PTC.8 However, current research has mainly focused on local immune resp","cbCaiuOnoIO9Q5uw","https://ap.wps.com/l/cbCaiuOnoIO9Q5uw","pdf",9875612,"English","# Abstract\n# Introduction\n# Methods","[{\"question\":\"What clinical problem does the study address?\",\"answer\":\"The study targets poor or variable response to radioactive iodine therapy after surgery for papillary thyroid carcinoma, aiming to predict efficacy before RAIT.\"},{\"question\":\"How were patients grouped for analysis?\",\"answer\":\"Patients were categorized into excellent response (ER) and nonexcellent response (NER) groups based on post-RAIT imaging/thyroglobulin antibody status and thyroglobulin and TSH-stimulated thyroglobulin thresholds.\"},{\"question\":\"What biomarkers and strategy were proposed to predict RAIT outcomes?\",\"answer\":\"The researchers identified that higher pre-RAIT HGF levels relate to worse disease-free survival and immune infiltration, and they propose a serum protein panel (FASLG, CXCL12, HGF) and a predictive model integrating baseline proteomic patterns with lymphocyte subset profiles.\"}]","Multiplex Immune Profiling Reveals the Role of Serum Immune Proteomics in Predicting Response to Radioiodine after Total Resection of Papillary Thyroid Carcinoma | PDF",1790701408,48]