de Barros E Lima Bueno Rafaela, Ramão Anelisa, Pinheiro Daniel Guariz, Alves Cleidson Padua, Kannen Vinicius, Jungbluth Achim A, de Araújo Luiza Ferreira, Muys Bruna Rodrigues, Fonseca Aline Simoneti, Plaça Jessica Rodrigues, Panepucci Rodrigo Alexandre, Neder Luciano, Saggioro Fabiano P, Mamede Rui Celso M, Figueiredo David Livingstone Alves, Silva Wilson Araújo
Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirão Preto, SP, CEP: 14049-900, Brazil.
National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, SP, CEP: 14051-140, Brazil.
Tumour Biol. 2016 Nov;37(11):15087-15096. doi: 10.1007/s13277-016-5356-8. Epub 2016 Sep 22.
Laryngeal squamous cell carcinoma (LSCC) is a very aggressive cancer, considered to be a subtype of the head and neck squamous cell carcinoma (HNSCC). Despite significant advances in the understanding and treatment of cancer, prognosis of patients with LSCC has not improved recently. In the present study, we sought to understand better the genetic mechanisms underlying LSCC development. Thirty-two tumor samples were collected from patients undergoing surgical resection of LSCC. The samples were submitted to whole-genome cDNA microarray analysis aiming to identify genetic targets in LSCC. We also employed bioinformatic approaches to expand our findings using the TCGA database and further performed functional assays, using human HNSCC cell lines, to evaluate viability, cell proliferation, and cell migration after silencing of selected genes. Eight members of the homeobox gene family (HOX) were identified to be overexpressed in LSCC samples when compared to normal larynx tissue. Quantitative RT-PCR analysis validated the overexpression of HOX gene family members in LSCC. Receiver operating characteristic (ROC) statistical method curve showed that the expression level of seven members of HOX gene family can distinguish tumor from nontumor tissue. Correlation analysis of clinical and gene expression data revealed that HOXC8 and HOXD11 genes were associated with the differentiation degree of tumors and regional lymph node metastases, respectively. Additionally, siRNA assays confirmed that HOXC8, HOXD10, and HOXD11 genes might be critical for cell colony proliferation and cell migration. According to our findings, several members of the HOX genes were overexpressed in LSCC samples and seem to be required in biological processes involved in tumor development. This suggests that HOX genes might play a critical role in the physiopathology of LSCC tumors.
喉鳞状细胞癌（LSCC）是一种侵袭性很强的癌症，被认为是头颈部鳞状细胞癌（HNSCC）的一种亚型。尽管在癌症的认识和治疗方面取得了重大进展，但LSCC患者的预后最近并未得到改善。在本研究中，我们试图更好地了解LSCC发生的遗传机制。从接受LSCC手术切除的患者中收集了32个肿瘤样本。将这些样本进行全基因组cDNA微阵列分析，旨在确定LSCC中的遗传靶点。我们还采用生物信息学方法，利用TCGA数据库扩展我们的研究结果，并进一步使用人类HNSCC细胞系进行功能测定，以评估选定基因沉默后的细胞活力、细胞增殖和细胞迁移。与正常喉组织相比，发现同源框基因家族（HOX）的8个成员在LSCC样本中过表达。定量RT-PCR分析验证了HOX基因家族成员在LSCC中的过表达。受试者工作特征（ROC）统计方法曲线显示，HOX基因家族7个成员的表达水平可区分肿瘤组织和非肿瘤组织。临床和基因表达数据的相关性分析表明，HOXC8和HOXD11基因分别与肿瘤的分化程度和区域淋巴结转移有关。此外，siRNA检测证实，HOXC8、HOXD10和HOXD11基因可能对细胞集落增殖和细胞迁移至关重要。根据我们的研究结果，HOX基因的几个成员在LSCC样本中过表达，似乎在肿瘤发生的生物学过程中是必需的。这表明HOX基因可能在LSCC肿瘤的病理生理学中起关键作用。
