2014年10月10日 訊 /生物谷BIOON/ --近日研究發現，蛋白質CLIP2 的表達了提供一項關於放射是否引起乳頭狀甲狀腺癌信息。通過這一發現科學家們確定了一個診斷癌症的新的生物標誌物。他們的發現發表在《致癌基因》雜誌上。
科學家們的研究能夠證實，CLIP2作為放射標誌物在通過放射性碘輻射後基因活性和蛋白表達量同時增加。CLIP2在通過射線照射甲狀腺腫瘤後似乎顯得特別重要。Martin Selmansberger博士帶領的團隊研究發現高水平的CLIP2含量和曾經通過放射治療乳頭狀甲狀腺瘤的患者之間有一定的關係。「在我們的研究中，我們能夠驗證在三組不同原因的甲狀腺癌患者的研究人群中，輻射相關的CLIP2的蛋白水平表達量的不同。」第一作者Selmansberger說道。
「CLIP2作為輻射標誌物，使我們能夠區分輻射誘導甲狀腺癌和散發甲狀腺癌的區別。」研究人員He補充道。在他們的研究中，科學家們開發了一種標準化的方法來確定CLIP2生物標誌物的重要性。「這種生物標記的作用是幫助我們得出有關腫瘤發展的機制和評估暴露於高水平輻射後患甲狀腺癌的風險的結論。例如，驗證輻射事故發生後患甲狀腺癌的結果。」He說道。
有關CLIP2能夠使甲狀腺致癌這一理論至今是未知的。重建的CLIP2調控基因顯示CLIP2參與基本的致癌過程，因此會促進腫瘤的惡化。（生物谷Bioon.com）
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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.