Almstrup Kristian, Leffers Henrik, Lothe Ragnhild A, Skakkebaek Niels E, Sonne Si B, Nielsen John E, Rajpert-De Meyts Ewa, Skotheim Rolf I
University Department of Growth and Reproduction, Rigshospitalet, Section GR-5064, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Int J Androl. 2007 Aug;30(4):292-302; discussion 303. doi: 10.1111/j.1365-2605.2007.00758.x. Epub 2007 May 7.
The carcinoma in situ (CIS) stage is the common precursor of testicular germ cell tumours (TGCTs) that arise in young adults. Within the past decade genome wide gene expression tools have been developed and have greatly advanced the insight into the biology of TGCTs. Two independent data sets on global gene expression in testicular CIS have been previously published. We have merged the two data sets on CIS samples (n = 6) and identified the shared gene expression signature in relation to expression in normal testis. Among the top-20 highest expressed genes, one-third was transcription factors and the list included some 'novel' CIS markers (i.e. DOCK11 and ANXA3). Genes related to biological terms 'nucleic acid binding' and 'translational activity' (e.g. transcription factors and ribosomal proteins, respectively) were consistently and significantly over-represented. Some of the significantly over-expressed genes in CIS cells were selected for validation by RT-PCR (IFI16, DOCK11, and ANXA3), immunohistochemistry (HLXB9), or in situ hybridization (IFI16). High-level analysis utilizing the Ingenuity pathway analysis tool indicated that networks relating to 'gene expression in cancer' and 'embryonic development' were significantly altered and could collectively affect cellular pathways like the WNT signalling cascade, which thus may be disrupted in testicular CIS. The merged CIS data from two different microarray platforms, to our knowledge, provide the most precise CIS gene expression signature to date.
原位癌（CIS）阶段是年轻成年男性发生的睾丸生殖细胞肿瘤（TGCT）常见的前驱病变。在过去十年中，全基因组基因表达工具得到了发展，极大地推进了对TGCT生物学特性的认识。此前已经发表了两个关于睾丸原位癌全基因组基因表达的独立数据集。我们将两个关于原位癌样本（n = 6）的数据集进行了合并，并确定了与正常睾丸表达相关的共享基因表达特征。在前20个高表达基因中，三分之一是转录因子，其中包括一些“新型”原位癌标志物（即DOCK11和ANXA3）。与生物学术语“核酸结合”和“翻译活性”相关的基因（分别例如转录因子和核糖体蛋白）持续且显著富集。通过逆转录聚合酶链反应（RT-PCR，检测IFI16、DOCK11和ANXA3）、免疫组织化学（检测HLXB9）或原位杂交（检测IFI16），对原位癌细胞中一些显著过表达的基因进行了验证。利用Ingenuity通路分析工具进行的高级分析表明，与“癌症中的基因表达”和“胚胎发育”相关的网络发生了显著改变，并可能共同影响细胞通路，如WNT信号级联反应，因此在睾丸原位癌中可能受到破坏。据我们所知，来自两个不同微阵列平台的合并原位癌数据提供了迄今为止最精确的原位癌基因表达特征。
