Abstract
OBJECTIVE: To investigate the expression of the TLR2/NF-κB signaling pathway and the Aggregate Index of Systemic Inflammation (AISI) in patients with papillary thyroid carcinoma (PTC) and to evaluate their clinical relevance to prognosis. METHODS: In this retrospective study, we analyzed surgically resected tumor tissue samples from 273 patients with PTC (PTC group) and paired adjacent non-tumorous tissues (PT group), as well as 104 nodular goiter tissues (NG group). The AISI values, along with the positive rates and mRNA expression levels of TLR2, MyD88, and NF-κB, were compared among the three groups. Differences in these indicators were compared across PTC patients with different clinicopathologic features. All PTC patients were followed up for three years and categorized into a survival group (n = 70) and a death group (n = 203) based on prognosis, and between-group comparisons were performed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the prognostic performance of each indicator. Kaplan-Meier survival curves were generated to compare overall survival between high- and low-expression subgroups stratified by TLR2, MyD88, NF-κB mRNA and AISI levels. Cox regression analysis was conducted to identify independent prognostic factors in PTC. RESULTS: Compared to the NG and PT groups, the PTC group showed higher AISI values, and protein positivity and mRNA expression of TLR2, MyD88, and NF-κB (all P<0.05). In the PTC group, the expression levels of these biomarkers and AISI values differed significantly according to tumor stage, lymph node metastasis, degree of differentiation, and extraglandular extension (P<0.05). Significant differences in differentiation grade, lymph node metastasis, extrathyroidal extension, TLR2, MyD88, NF-κB mRNA, and AISI levels were observed between the survival and death groups (P<0.05). The AUC values for predicting patient prognosis based on TLR2, MyD88, NF-κB mRNA, and AISI individually or in combination were 0.802, 0.795, 0.799, 0.815, and 0.818, respectively. Patients with low expression levels of TLR2, MyD88, NF-κB mRNA, and AISI had significantly longer overall survival compared to those with high expression levels (P<0.05). CONCLUSION: Poor differentiation, extrathyroidal extension, and high AISI expression are independent factors for poor PTC prognosis. The TLR2/NF-κB signaling pathway and AISI are closely associated with tumor progression and have prognostic value.