Multiplex Immune Profiling Reveals the Role of Serum Immune Proteomics in Predicting Response to Radioiodine after Total Resection of Papillary Thyroid Carcinoma

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.