Oncogene：生物标志物揭示癌症发病原因
来源：生物谷 2014-10-10 14:472014年10月10日 讯 /生物谷BIOON/ --近日研究发现，蛋白质CLIP2 的表达了提供一项关于放射是否引起乳头状甲状腺癌信息。通过这一发现科学家们确定了一个诊断癌症的新的生物标志物。他们的发现发表在《致癌基因》杂志上。
科学家们的研究能够证实，CLIP2作为放射标志物在通过放射性碘辐射后基因活性和蛋白表达量同时增加。CLIP2在通过射线照射甲状腺肿瘤后似乎显得特别重要。Martin Selmansberger博士带领的团队研究发现高水平的CLIP2含量和曾经通过放射治疗乳头状甲状腺瘤的患者之间有一定的关系。“在我们的研究中，我们能够验证在三组不同原因的甲状腺癌患者的研究人群中，辐射相关的CLIP2的蛋白水平表达量的不同。”第一作者Selmansberger说道。
“CLIP2作为辐射标志物，使我们能够区分辐射诱导甲状腺癌和散发甲状腺癌的区别。”研究人员He补充道。在他们的研究中，科学家们开发了一种标准化的方法来确定CLIP2生物标志物的重要性。“这种生物标记的作用是帮助我们得出有关肿瘤发展的机制和评估暴露于高水平辐射后患甲状腺癌的风险的结论。例如，验证辐射事故发生后患甲状腺癌的结果。”He说道。
有关CLIP2能够使甲状腺致癌这一理论至今是未知的。重建的CLIP2调控基因显示CLIP2参与基本的致癌过程，因此会促进肿瘤的恶化。（生物谷Bioon.com）
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doi:10.1038/onc.2014.311
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CLIP2 as radiation biomarker in papillary thyroid carcinoma
M Selmansberger, A Feuchtinger, L Zurnadzhy, A Michna, J C Kaiser, M Abend, A Brenner, T Bogdanova, A Walch, K Unger, H Zitzelsberger and J Hess
A substantial increase in papillary thyroid carcinoma (PTC) among children exposed to the radioiodine fallout has been one of the main consequences of the Chernobyl reactor accident. Recently, the investigation of PTCs from a cohort of young patients exposed to the post-Chernobyl radioiodine fallout at very young age and a matched nonexposed control group revealed a radiation-specific DNA copy number gain on chromosomal band 7q11.23 and the radiation-associated mRNA overexpression of CLIP2. In this study, we investigated the potential role of CLIP2 as a radiation marker to be used for the individual classification of PTCs into CLIP2-positive and -negative cases—a prerequisite for the integration of CLIP2 into epidemiological modelling of the risk of radiation-induced PTC. We were able to validate the radiation-associated CLIP2 overexpression at the protein level by immunohistochemistry (IHC) followed by relative quantification using digital image analysis software (P=0.0149). Furthermore, we developed a standardized workflow for the determination of CLIP2-positive and -negative cases that combines visual CLIP2 IHC scoring and CLIP2 genomic copy number status. In addition to the discovery cohort (n=33), two independent validation cohorts of PTCs (n=115) were investigated. High sensitivity and specificity rates for all three investigated cohorts were obtained, demonstrating robustness of the developed workflow. To analyse the function of CLIP2 in radiation-associated PTC, the CLIP2 gene regulatory network was reconstructed using global mRNA expression data from PTC patient samples. The genes comprising the first neighbourhood of CLIP2 (BAG2, CHST3, KIF3C, NEURL1, PPIL3 and RGS4) suggest the involvement of CLIP2 in the fundamental carcinogenic processes including apoptosis, mitogen-activated protein kinase signalling and genomic instability. In our study, we successfully developed and independently validated a workflow for the typing of PTC clinical samples into CLIP2-positive and CLIP2-negative and provided first insights into the CLIP2 interactome in the context of radiation-associated PTC.
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