# Gene Expression Analysis of Papillary Thyroid Carcinoma With Lymph Node Metastasis and Radioiodine Refractivity

## TL;DR

This study compares gene expression in aggressive thyroid cancer cases that resist treatment with those that respond well, identifying key differences that could help develop better therapies.

## Contribution

The study presents a novel microarray-based gene expression dataset for RAI-refractory papillary thyroid carcinoma with lymph node metastasis.

## Key findings

- RAI-refractory PTC showed significant downregulation of thyroid hormone synthesis genes like TPO, DIO1, and SLC26A4.
- TG exhibited variable expression, indicating its complex role in PTC progression.
- Disrupted metabolic and immune-related pathways were identified in RAI-refractory PTC.

## Abstract

Background/aim: Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer (TC) and is generally associated with a favorable prognosis. Nevertheless, aggressive variants of PTC that exhibit metastasis and resistance to radioiodine (RAI) therapy present significant clinical challenges. This study sought to generate a preliminary dataset on gene expression in RAI-refractory PTC using microarray analysis.

Materials and methods: Fresh frozen thyroid tissues were collected from PTC patients without lymph node metastasis and RAI avidity (n = 5), PTC patients with lymph node metastasis and RAI refractoriness (n = 5), and adjacent normal thyroid tissues (n = 4). The samples were cryosectioned, stained with hematoxylin and eosin, and confirmed by a pathologist. Nucleic acids were extracted using the AllPrep DNA/RNA/miRNA Universal Kit (Qiagen, Germany), and RNA quantity, purity, and integrity were assessed. RNA samples were amplified, labelled using the Agilent Low Input Quick Amp Labeling Kit (Agilent Technologies, Santa Clara, CA, US), and purified using the RNeasy Mini Kit (Qiagen). Cy3-labelled cRNA was fragmented and hybridized to Agilent SurePrint G3 Human GE v3 8 × 60 K microarray slides. Data were analyzed using AltAnalyze software and the iDEP web application.

Results: Our results revealed distinct expression patterns between RAI-avid and RAI-refractory PTC, with significant downregulation observed in key thyroid hormone synthesis genes, such as TPO, DIO1, and SLC26A4, across both groups. Notably, TG showed a variable expression pattern, suggesting its complex role in PTC pathophysiology. Pathway analysis highlighted the disruption of metabolic and immune-related pathways, emphasizing the altered physiological state of RAI-refractory PTC.

Conclusion: This study provides essential insights into the molecular underpinnings of RAI resistance in PTC and offers a foundation for future research aimed at developing targeted therapies that could enhance treatment efficacy and patient outcomes.