# Identification of risk factors for high-risk dedifferentiation in papillary thyroid carcinoma and construction of discriminative model

## TL;DR

This study identifies risk factors for high-risk dedifferentiation in thyroid cancer and builds a model to predict it, offering potential for better treatment strategies.

## Contribution

The study constructs a novel discriminative model for high-risk dedifferentiation in papillary thyroid carcinoma using TDS, disease duration, and subtype.

## Key findings

- The thyroid differentiation score (TDS) is significantly associated with progression-free interval in PTC patients.
- Disease duration and PTC subtype are key factors influencing dedifferentiation, with a nomogram model showing improved discrimination.
- CD55 is a central gene in dedifferentiation, with increased expression in high-risk PTC subtypes.

## Abstract

We initially found that the thyroid differentiation score (TDS) was associated with the prognosis of papillary thyroid carcinoma (PTC) patients. Therefore, this study aimed to investigate the influencing factors and construct a discriminative model of high-risk dedifferentiation, and to explore the possible mechanisms.

Data were sourced from the TCGA database. The influences of the TDS, tumor mutation burden, and immune score on the progression-free interval (PFI) were assessed by the Kaplan-Meier method and multivariable Cox regression. Then, logistic regression analyses were utilized to explore the factors of dedifferentiation and a nomogram model was conducted. Additionally, differentially expressed genes (DEGs) were identified using RNA sequencing data, while their regulatory pathways were determined by the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, the differential expression of key genes of major pathways was explored.

This study included 391 PTC patients. After analyzing the influences of the three indicators on survival, only TDS showed an association with PFI. Multivariable logistic analysis revealed that the disease duration and PTC subtypes influenced dedifferentiation. The nomogram model based on these two variables showed improved discriminative capability. The study identified 17 overlapping DEGs associated with the dedifferentiation and three primary enrichment pathways, with complement and coagulation cascade pathways being the most significant (P<0.001). The central gene was CD55, which showed high expression in high-risk dedifferentiated and tall cell PTC, and the expression level increased as the disease progressed.

This research may contribute to promising identifying high-risk dedifferentiated PTC and also provide a potential therapeutic target.