Gasparotto Daniela, Polesel Jerry, Marzotto Alessandra, Colladel Roberta, Piccinin Sara, Modena Piergiorgio, Grizzo Alessandra, Sulfaro Sandro, Serraino Diego, Barzan Luigi, Doglioni Claudio, Maestro Roberta
Unit of Experimental Oncology 1, CRO National Cancer Institute, Aviano, Italy.
Oncotarget. 2011 Dec;2(12):1165-75. doi: 10.18632/oncotarget.390.
Head and neck squamous cell carcinomas (HNSCC) are a heterogeneous group of tumors with variable presentation and clinical behavior. Despite improvements in surgical and radiation therapy techniques, the 5-year survival rate has not improved significantly over the past decades. Thus, there is an urgent need to identify novel markers that may allow for the development of personalized therapeutic approaches. In the present study we evaluated the prognostic role of the expression of genes related to the induction of epithelial mesenchymal transition (EMT). To this aim, a consecutive series of 69 HNSCC were analyzed for the expression of TWIST1, TWIST2, SNAI1, SNAI2, E-Cadherin, N-Cadherin and Vimentin.TWIST1, TWIST2, SNAI1 and SNAI2 were significantly overexpressed in HNSCC, with TWIST2, SNAI1 and SNAI2 being more markedly increased in tumors compared to normal mucosae. The expression of TWIST1 and SNAI2 was associated with upregulation of mesenchymal markers, but failed to correlate with pathological parameters or clinical behaviour. In contrast, we found that upregulation of TWIST2, which was independent of the activation of a mesenchymal differentiation program, correlated with poor differentiation grade (p=0.016) and shorter survival (p=0.025), and identifies a subset of node-positive oral cavity/pharynx cancer patients with very poor prognosis (p less than 0.001). Overall our study suggests that the assessment of TWIST2 expression might help to stratify HNSCC patients for risk of disease progression, pointing to TWIST2 as a potential prognostic marker.
头颈部鳞状细胞癌（HNSCC）是一组异质性肿瘤，其表现和临床行为各不相同。尽管手术和放射治疗技术有所改进，但在过去几十年中，5年生存率并未显著提高。因此，迫切需要识别新的标志物，以便开发个性化治疗方法。在本研究中，我们评估了与上皮-间质转化（EMT）诱导相关基因表达的预后作用。为此，我们连续分析了69例HNSCC患者的TWIST1、TWIST2、SNAI1、SNAI2、E-钙黏蛋白、N-钙黏蛋白和波形蛋白的表达情况。TWIST1、TWIST2、SNAI1和SNAI2在HNSCC中显著过表达，与正常黏膜相比，TWIST2、SNAI1和SNAI2在肿瘤中增加更为明显。TWIST1和SNAI2的表达与间质标志物的上调相关，但与病理参数或临床行为无关。相比之下，我们发现TWIST2的上调与低分化等级（p=0.016）和较短生存期（p=0.025）相关，且与间充质分化程序的激活无关，它可识别出一组预后极差的口腔/咽癌淋巴结阳性患者（p<0.001）。总体而言，我们的研究表明，评估TWIST2表达可能有助于对HNSCC患者进行疾病进展风险分层，提示TWIST2作为一种潜在的预后标志物。
