Tyszkiewicz Tomasz, Jarzab Michal, Szymczyk Cezary, Kowal Monika, Krajewska Jolanta, Jaworska Magdalena, Fraczek Marcin, Krajewska Anna, Hadas Ewa, Swierniak Michal, Markowski Jaroslaw, Lange Dariusz, Poltorak Stanislaw, Wiench Malgorzata, Krecicki Tomasz, Jarzab Jerzy, Maciejewski Adam
Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch.
Folia Histochem Cytobiol. 2014;52(2):79-89. doi: 10.5603/FHC.2014.0018.
Epidermal differentiation complex (EDC) comprises a number of genes associated with human skin diseases including psoriasis, atopic dermatitis and hyperkeratosis. These genes have also been linked to numerous cancers, among them skin, gastric, colorectal, lung, ovarian and renal carcinomas. The involvement of EDC components encoding S100 proteins, small proline-rich proteins (SPRRs) and other genes in the tumorigenesis of head and neck squamous cell cancer (HNSCC) has been previously suggested. The aim of the study was to systematically analyze the expression of EDC components on the transcript level in HNSCC. Tissue specimens from 93 patients with HNC of oral cavity and 87 samples from adjacent or distant grossly normal oral mucosawere analyzed. 48 samples (24 tumor and 24 corresponding surrounding tissue) were hybridized to Affymetrix GeneChip Human 1.0 ST Arrays. For validation by quantitative real-time PCR (QPCR) the total RNA from all180 samples collected in the study was analyzed with Real-Time PCR system and fluorescent amplicon specific-probes. Additional set of samples from 14 patients with laryngeal carcinoma previously obtained by HG-U133 Plus 2.0 microarray was also included in the analyses. The expression of analyzed EDC genes was heterogeneous. Two transcripts (S100A1 and S100A4) were significantly down-regulated in oral cancer when compared to normal mucosa (0.69 and 0.36-fold change, respectively), showing an opposite pattern of expression to the remaining S100 genes. Significant up-regulation in tumors was found for S100A11, S100A7, LCE3D, S100A3 and S100A2 genes. The increased expression of S100A7 was subsequently validated by QPCR, confirming significant differences. The remaining EDC genes, including all encoding SPRR molecules, did not show any differences between oral cancer and normal mucosa. The observed differences were also assessed in the independent set of laryngeal cancer samples, confirming the role of S100A3 and LCE3D transcripts in HNC. In HNC of oral cavity only one family of EDC genes (S100 proteins) showed significant cancer-related differences. A number of other transcripts which showed altered expression in HNC require further validation.
表皮分化复合体（EDC）由许多与人类皮肤疾病相关的基因组成，这些疾病包括银屑病、特应性皮炎和角化过度。这些基因还与多种癌症有关，其中包括皮肤癌、胃癌、结直肠癌、肺癌、卵巢癌和肾癌。先前已有研究表明，编码S100蛋白、富含脯氨酸的小分子蛋白（SPRRs）和其他基因的EDC成分参与头颈部鳞状细胞癌（HNSCC）的肿瘤发生过程。本研究的目的是系统分析EDC成分在HNSCC转录水平上的表达情况。对93例口腔HNC患者的组织标本和87例来自相邻或远处大体正常口腔黏膜的样本进行了分析。48个样本（24个肿瘤样本和24个相应的周围组织样本）与Affymetrix GeneChip Human 1.0 ST阵列进行杂交。为了通过定量实时PCR（QPCR）进行验证，使用实时PCR系统和荧光扩增子特异性探针分析了本研究收集的所有180个样本的总RNA。分析还纳入了先前通过HG-U133 Plus 2.0微阵列获得的14例喉癌患者的另一组样本。所分析的EDC基因的表达具有异质性。与正常黏膜相比，两种转录本（S100A1和S100A4）在口腔癌中显著下调（变化倍数分别为0.69和0.36），其表达模式与其余S100基因相反。发现S100A11、S100A7、LCE3D、S100A3和S100A2基因在肿瘤中显著上调。随后通过QPCR验证了S100A7表达的增加，证实了显著差异。其余的EDC基因，包括所有编码SPRR分子的基因，在口腔癌和正常黏膜之间未显示出任何差异。在独立的喉癌样本组中也评估了观察到的差异，证实了S100A3和LCE3D转录本在HNC中的作用。在口腔HNC中，只有一个EDC基因家族（S100蛋白）显示出与癌症相关的显著差异。许多在HNC中表达改变的其他转录本需要进一步验证。
