Vázquez-Ortíz Guelaguetza, Ciudad Carlos J, Piña Patricia, Vazquez Karla, Hidalgo Alfredo, Alatorre Brenda, Garcia Jose A, Salamanca Fabio, Peralta-Rodriguez Raul, Rangel Angélica, Salcedo Mauricio
Oncogenomics Laboratory, Oncological Diseases Research Unit, Oncology Hospital, 21st Century National Medical Center, Mexico City, Mexico.
Arch Med Res. 2005 Sep-Oct;36(5):448-58. doi: 10.1016/j.arcmed.2005.04.016.
One of the most frequent malignancies in women worldwide is carcinoma of the uterine cervix. High-risk human papillomavirus (HPV) infection is considered the most important etiological factor of uterine cervical cancer. Our aim was to identify novel cellular genes that could potentially act as predictive molecular markers for human cervical cancer by means of cDNA arrays.
We used cDNA arrays to examine the expression profiles of six cell lines derived from human cervical cancer, three HPV+ tumor samples and three normal (HPV-) epithelium tissues. Data normalization was performed and the top overexpressed genes were obtained. Hierarchical cluster was performed and, to validate some of the differentially expressed genes between normal and carcinogenic samples, semi-quantitative RT-PCR, in situ hybridization and immunohistochemistry were performed in tissue samples.
Four genes were demonstrated to be consistently overexpressed in invasive cervical cancer biopsies; three novel genes not previously related to cervical cancer: MMP10, Lamc2 and Claudin 1. Moreover, overexpression of IL6 and VEGF was corroborated.
The identification of characteristic molecular changes in cervical cells by carcinogenesis and HPV infection can lead to a better understanding of cervical cancer. cDNA arrays are beginning to provide new possible molecular markers for prognosis and diagnosis. This technology could eventually help to elucidate the biological differences of the particular mechanisms associated with each different HPV-type infection and those with a poor prognosis.
子宫颈癌是全球女性中最常见的恶性肿瘤之一。高危型人乳头瘤病毒（HPV）感染被认为是子宫颈癌最重要的病因。我们的目的是通过cDNA阵列鉴定可能作为人类宫颈癌预测分子标志物的新细胞基因。
我们使用cDNA阵列检测来自人宫颈癌的六种细胞系、三个HPV阳性肿瘤样本和三个正常（HPV阴性）上皮组织的表达谱。进行数据归一化并获得高表达基因。进行层次聚类，为验证正常样本和致癌样本之间一些差异表达的基因，在组织样本中进行半定量RT-PCR、原位杂交和免疫组化。
四个基因在浸润性宫颈癌活检中持续高表达；三个以前与宫颈癌无关的新基因：基质金属蛋白酶10（MMP10）、层粘连蛋白γ2（LAMC2）和紧密连接蛋白1（Claudin 1）。此外，白细胞介素6（IL6）和血管内皮生长因子（VEGF）的高表达得到证实。
通过致癌作用和HPV感染鉴定宫颈细胞中的特征性分子变化有助于更好地理解宫颈癌。cDNA阵列开始为预后和诊断提供新的可能的分子标志物。这项技术最终可能有助于阐明与每种不同HPV类型感染相关的特定机制以及预后不良机制的生物学差异。
