Raudenska Martina, Sztalmachova Marketa, Gumulec Jaromir, Fojtu Michaela, Polanska Hana, Balvan Jan, Feith Marek, Binkova Hana, Horakova Zuzana, Kostrica Rom, Kizek Rene, Masarik Michal
Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00, Brno, Czech Republic.
Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-616 00, Brno, Czech Republic.
Tumour Biol. 2015 Dec;36(12):9929-39. doi: 10.1007/s13277-015-3755-x. Epub 2015 Jul 14.
Even with significant advances in operative skills and adjuvant therapies, the overall survival of patients suffering with head and neck squamous cancers (HNSCC) is unsatisfactory. Accordingly, no clinically useful prognostic biomarkers have been found yet for HNSCC. Many studies analysed the expression of potential markers in tumour tissues compared to adjacent tissues. Nevertheless, due to the sharing of the same microenvironment, adjacent tissues show molecular similarity to tumour tissues. Thus, gene expression patterns of 94 HNSCC tumorous tissues were compared with 31 adjacent tissues and with 10 tonsillectomy specimens of non-cancer individuals. The genes analysed at RNA level using quantitative RT-PCR and correlated with clinico-pathological conditions were as follows: EGF, EGFR, MKI67, BCL2, BAX, FOS, JUN, TP53, VEGF, FLT1, MMP2, MMP9, MT1A and MT2A. The elevated MT2A, BAX, EGF and JUN expression was associated with the influence of tumour cells on the rearrangement of healthy tissues, as well as a significant shift in the BAX/BCL2 ratio. Our investigation also indicated that adjacent tissues play an important role in cancerogenesis by releasing several tumour-supporting factors such as EGF. A gradual increase in the metallothionein expression, from the lowest one in tonsillectomy samples to the highest ones in tumour samples, suggests that MT expression might be tissue reaction to the presence of tumour cells. The results of this study confirmed the significance of metallothionein in tumori-genesis and gave evidences for its use as a potential HNSCC biomarker. Furthermore, this study highlighted the importance of histologically normal tumour-adjacent tissue in prediction of HNSCC progress.
尽管手术技巧和辅助治疗取得了显著进展,但头颈部鳞状细胞癌(HNSCC)患者的总体生存率仍不尽人意。因此,尚未发现对HNSCC具有临床实用价值的预后生物标志物。许多研究分析了肿瘤组织与相邻组织中潜在标志物的表达情况。然而,由于共享相同的微环境,相邻组织与肿瘤组织表现出分子相似性。因此,将94例HNSCC肿瘤组织的基因表达模式与31例相邻组织以及10例非癌个体的扁桃体切除标本进行了比较。使用定量RT-PCR在RNA水平分析并与临床病理状况相关的基因如下:EGF、EGFR、MKI67、BCL2、BAX、FOS、JUN、TP53、VEGF、FLT1、MMP2、MMP9、MT1A和MT2A。MT2A、BAX、EGF和JUN表达的升高与肿瘤细胞对健康组织重排的影响以及BAX/BCL2比值的显著变化有关。我们的研究还表明,相邻组织通过释放几种肿瘤支持因子(如EGF)在肿瘤发生中起重要作用。金属硫蛋白表达从扁桃体切除样本中的最低水平逐渐增加到肿瘤样本中的最高水平,表明MT表达可能是组织对肿瘤细胞存在的反应。本研究结果证实了金属硫蛋白在肿瘤发生中的重要性,并为其作为潜在的HNSCC生物标志物提供了证据。此外,本研究强调了组织学正常的肿瘤相邻组织在预测HNSCC进展中的重要性。