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对人乳头瘤病毒(HPV)阳性和阴性的头颈部鳞状细胞癌以及配对的正常黏膜进行分析,发现细胞周期蛋白D1失调及细胞周期蛋白D2的代偿作用。

Analysis of HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinomas and Paired Normal Mucosae Reveals Cyclin D1 Deregulation and Compensatory Effect of Cyclin D2.

作者信息

Novotný Jiří, Bandúrová Veronika, Strnad Hynek, Chovanec Martin, Hradilová Miluše, Šáchová Jana, Šteffl Martin, Grušanović Josipa, Kodet Roman, Pačes Václav, Lacina Lukáš, Smetana Karel, Plzák Jan, Kolář Michal, Vomastek Tomáš

机构信息

Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics of the Czech Academy of Sciences, 142 20 Prague, Czech Republic.

Department of Informatics and Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology, 160 00 Prague, Czech Republic.

出版信息

Cancers (Basel). 2020 Mar 26;12(4):792. doi: 10.3390/cancers12040792.

Abstract

Aberrant regulation of the cell cycle is a typical feature of all forms of cancer. In head and neck squamous cell carcinoma (HNSCC), it is often associated with the overexpression of cyclin D1 (). However, it remains unclear how expression changes between tumor and normal tissues and whether human papillomavirus (HPV) affects differential expression. Here, we evaluated the expression of D-type cyclins in a cohort of 94 HNSCC patients of which 82 were subjected to whole genome expression profiling of primary tumors and paired normal mucosa. Comparative analysis of paired samples showed that was upregulated in 18% of HNSCC tumors. Counterintuitively, was downregulated in 23% of carcinomas, more frequently in HPV-positive samples. There was no correlation between the change in D-type cyclin expression and patient survival. Intriguingly, among the tumors with downregulated , one-third showed an increase in cyclin D2 () expression. On the other hand, one-third of tumors with upregulated showed a decrease in . Collectively, we have shown that was frequently downregulated in HNSCC tumors. Furthermore, regardless of the HPV status, our data suggested that a change in expression was alleviated by a compensatory change in expression.

摘要

细胞周期的异常调控是所有癌症形式的典型特征。在头颈部鳞状细胞癌(HNSCC)中,它通常与细胞周期蛋白D1()的过表达相关。然而,其在肿瘤组织和正常组织之间的表达变化以及人乳头瘤病毒(HPV)是否影响差异表达仍不清楚。在此,我们评估了94例HNSCC患者队列中D型细胞周期蛋白的表达,其中82例患者接受了原发性肿瘤和配对正常黏膜的全基因组表达谱分析。配对样本的比较分析显示,18%的HNSCC肿瘤中 上调。与直觉相反,23%的癌组织中 下调,在HPV阳性样本中更常见。D型细胞周期蛋白表达的变化与患者生存率之间没有相关性。有趣的是,在 下调的肿瘤中,三分之一显示细胞周期蛋白D2()表达增加。另一方面, 上调的肿瘤中有三分之一显示 表达下降。总体而言,我们已表明在HNSCC肿瘤中 经常下调。此外,无论HPV状态如何,我们的数据表明 表达的变化通过 表达的代偿性变化得到缓解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3526/7226528/64cddab80b75/cancers-12-00792-g001.jpg

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