Comprehensive analysis for detecting radiation-specific molecules expressed during radiation-induced rat thyroid carcinogenesis

Autor: Hirokazu Kurohama, Hisayoshi Kondo, Miruki Yoshino, Masahiro Nakashima, Ko-ichiro Yoshiura, Mio Kishino, Yuka Yamaguchi, Norisato Mitsutake, Akira Kinoshita, Mutsumi Matsuu-Matsuyama, Katsuya Matsuda
Rok vydání: 2021
Předmět:
Male
endocrine system
Candidate gene
Neoplasms
Radiation-Induced
Carcinogenesis
Health
Toxicology and Mutagenesis
Thyroid Gland
medicine.disease_cause
thyroid
03 medical and health sciences
0302 clinical medicine
Gene expression
Biomarkers
Tumor
medicine
Animals
Radiology
Nuclear Medicine and imaging
Digital polymerase chain reaction
RNA
Messenger
Thyroid Neoplasms
Fundamental Radiation Science
Rats
Wistar
Thyroid cancer
030304 developmental biology
0303 health sciences
Radiation
Microarray analysis techniques
business.industry
Gene Expression Profiling
animal model
Thyroid
Reproducibility of Results
medicine.disease
Gene Expression Regulation
Neoplastic
CDKN1A
medicine.anatomical_structure
030220 oncology & carcinogenesis
Cancer research
AcademicSubjects/SCI00960
biomarker
RNA microarray
Biomarker (medicine)
AcademicSubjects/MED00870
business
Zdroj: Journal of Radiation Research
ISSN: 1349-9157
0449-3060
Popis: Although the association between radiation exposure and thyroid carcinogenesis is epidemiologically evident, ’true’ radiation-induced cancers cannot be identified from biological evidence of radiation-associated cases. To assess the individual risk for thyroid cancer due to radiation exposure, we aimed to identify biomarkers that are specifically altered during thyroid carcinogenesis after irradiation in a time-dependent manner in an animal model. Thyroid glands were obtained from rats (n = 175) at 6–16 months after local X-ray (0.1–4 Gy) irradiation of the neck at 7 weeks of age. The gene expression profile in thyroid glands was comprehensively analyzed using RNA microarray. Subsequently, the expression levels of the genes of interest were verified using droplet digital PCR (ddPCR). The expression level of candidate genes as biomarkers for irradiated thyroid was examined in a randomized, controlled, double-blind validation study (n = 19) using ddPCR. The incidence of thyroid cancer increased in a dose- and time-dependent manner and was 33% at 16 months after irradiation with 4 Gy. The Ki-67 labeling index in non-tumorous thyroid was significantly higher in the exposed group than in the control. Comprehensive analysis identified radiation-dependent alteration in 3329 genes. Among them, ddPCR revealed a stepwise increase in CDKN1A expression from early pre-cancerous phase in irradiated thyroid compared to that in the control. The irradiated thyroids were accurately distinguished (positive predictive value 100%, negative predictive value 69%) using 11.69 as the cut-off value for CDKN1A/β-actin. Thus, CDKN1A expression can be used as a biomarker for irradiated thyroid glands at the pre-cancerous phase.
Databáze: OpenAIRE
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