Biomarker Identification and Risk Prediction Model Development for Differentiated Thyroid Carcinoma Lung Metastasis Based on Primary Lesion Proteomics.

ABSTRACT

PURPOSE: The rising global high incidence of differentiated thyroid carcinoma (DTC) has led to a significant increase in patients presenting with lung metastasis of DTC (LMDTC). This population poses a significant challenge in clinical practice, necessitating the urgent development of effective risk stratification methods and predictive tools for lung metastasis. EXPERIMENTAL DESIGN: Through proteomic analysis of large samples of primary lesion and dual validation employing parallel reaction monitoring and IHC, we identified eight hub proteins as potential biomarkers. By expanding the sample size and conducting statistical analysis on clinical features and hub protein expression, we constructed three risk prediction models. RESULTS: This study identified eight hub proteins-SUCLG1/2, DLAT, IDH3B, ACSF2, ACO2, CYCS, and VDAC2-as potential biomarkers for predicting LMDTC risk. We developed and internally validated three risk prediction models incorporating both clinical characteristics and hub protein expression. Our findings demonstrated that the combined prediction model exhibited optimal predictive performance, with the highest discrimination (AUC 0.986) and calibration (Brier score 0.043). Application of the combined prediction model within a specific risk threshold (0-0.97) yielded maximal clinical benefit. Finally, we constructed a nomogram based on the combined prediction model. CONCLUSIONS: As a large sample size study in LMDTC research, the identification of biomarkers through primary lesion proteomics and the development of risk prediction models integrating clinical features and hub protein biomarkers offer valuable insights for predicting LMDTC and establishing personalized treatment strategies.