Comprehensive analysis for detecting radiation-specific molecules expressed during radiation-induced rat thyroid carcinogenesis.
Comprehensive analysis for detecting radiation-specific molecules expressed during radiation-induced rat thyroid carcinogenesis.
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DOI：
10.1093/jrr/rraa139
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发表时间：
2021-05-05
影响因子：
2
通讯作者：
Nakashima M
中科院分区：
文献类型：
--
作者：
Kurohama H;Matsuda K;Kishino M;Yoshino M;Yamaguchi Y;Matsuu-Matsuyama M;Kondo H;Mitsutake N;Kinoshita A;Yoshiura KI;Nakashima M
虽然辐射照射与甲状腺癌发生之间的关联在流行病学上是显而易见的，但无法从辐射相关病例的生物学证据中确定“真正的”辐射诱发癌症。为了评估由于辐射暴露而导致甲状腺癌的个体风险，我们的目的是在动物模型中以时间依赖性方式确定在辐射后甲状腺致癌过程中特异性改变的生物标志物。甲状腺取自7周龄时颈部局部X线（0.1-4戈伊）照射后6-16个月的大鼠（n = 175）。利用RNA微阵列技术对甲状腺组织基因表达谱进行了全面分析。随后，使用液滴数字PCR（ddPCR）验证目的基因的表达水平。在一项随机、对照、双盲验证研究（n = 19）中，使用ddPCR检查了作为辐照甲状腺生物标志物的候选基因的表达水平。甲状腺癌的发病率呈剂量和时间依赖性增加，在4戈伊照射后16个月为33%。在非肿瘤性甲状腺Ki-67标记指数显着高于接触组比对照组。综合分析确定了3329个基因的辐射依赖性改变。其中，ddPCR显示，与对照组相比，照射甲状腺中CDKN 1A的表达从早期癌前阶段开始逐步增加。使用11.69作为CDKN 1A/β-actin的截止值，可准确区分辐照甲状腺（阳性预测值100%，阴性预测值69%）。因此，CDKN 1A表达可用作癌前阶段辐射甲状腺的生物标志物。
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.
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年龄对大鼠甲状腺对电离辐射的敏感性的影响。
影响因子：
2
作者：
Matsuu-Matsuyama M;Shichijo K;Okaichi K;Kurashige T;Kondo H;Miura S;Nakashima M
通讯作者：
Nakashima M
影响因子：
6.4
作者：
Furukawa, Kyoji;Preston, Dale;Funamoto, Sachiyo;Yonehara, Shuji;Ito, Masahiro;Tokuoka, Shoji;Sugiyama, Hiromi;Soda, Midori;Ozasa, Kotaro;Mabuchi, Kiyohiko
通讯作者：
Mabuchi, Kiyohiko
影响因子：
5.6
作者：
Albi E;Cataldi S;Lazzarini A;Codini M;Beccari T;Ambesi-Impiombato FS;Curcio F
通讯作者：
Curcio F
影响因子：
4.7
作者：
Kaiser, Jan Christian;Meckbach, Reinhard;Jacob, Peter
通讯作者：
Jacob, Peter
影响因子：
3.4
作者：
Johnston, CJ;Williams, JP;Finkelstein, JN
通讯作者：
Finkelstein, JN