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Comprehensive analysis for detecting radiation-specific molecules expressed during radiation-induced rat thyroid
Hirokazu Kurohama1, Katsuya Matsuda1, Mio Kishino2
1Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Journal of Radiation Research
|May 12, 2021
Summary
Radiation exposure increases thyroid cancer risk in rats. CDKN1A gene expression serves as a reliable biomarker for detecting radiation-induced thyroid changes in the pre-cancerous phase, aiding early risk assessment.
Area of Science:
- Molecular biology
- Oncology
- Radiation research
Background:
- Radiation exposure is a known risk factor for thyroid cancer.
- Identifying specific biological markers for radiation-induced thyroid cancer is crucial for risk assessment.
- Current methods lack definitive biological evidence for radiation-associated thyroid cancers.
Purpose of the Study:
- To identify specific biomarkers for radiation-induced thyroid carcinogenesis.
- To investigate time- and dose-dependent alterations in gene expression following irradiation.
- To validate potential biomarkers in a preclinical setting.
Main Methods:
- Rats were subjected to X-ray irradiation (0.1-4 Gy) and thyroid glands collected 6-16 months post-irradiation.
- Comprehensive gene expression profiling using RNA microarray.
- Validation of candidate genes using droplet digital PCR (ddPCR) and a validation study.
Main Results:
- Thyroid cancer incidence increased with radiation dose and time, reaching 33% at 4 Gy/16 months.
- Elevated Ki-67 labeling index observed in non-tumorous thyroid tissue of irradiated rats.
- CDKN1A expression showed a stepwise increase from the pre-cancerous phase in irradiated thyroids.
- CDKN1A/β-actin ratio distinguished irradiated thyroids with high accuracy (PPV 100%, NPV 69%).
Conclusions:
- CDKN1A is a promising biomarker for detecting radiation-induced thyroid alterations in the pre-cancerous stage.
- This finding aids in the early identification and risk assessment of radiation-associated thyroid cancer.
- The study provides a biological basis for understanding radiation carcinogenesis in the thyroid.
