Chang Hui-Jen, Yang Ming-Je, Yang Yu-Hsiang, Hou Ming-Feng, Hsueh Er-Jung, Lin Shiu-Ru
School of Medical and Health Science, Fooyin University, Department of Medical Research, Foyyin University Hospital, Daliao Township, Kaohsiung County, Taiwan, ROC.
Oncol Rep. 2009 Nov;22(5):1119-27. doi: 10.3892/or_00000544.
Within the past decade, the incidence of breast cancer in Taiwan has been rising year after year. Breast cancer is the first most prevalent cancer and the fourth leading cause of cancer-related deaths among women in Taiwan. The early stage of breast cancer not only have a wider range of therapeutic options, but also obtain a higher success rate of therapy than those with advanced breast cancer. A test for tumor markers is the most convenient method to screen for breast cancer. However, the tumor markers currently available for breast cancer detection include carcinoembryonic antigen (CEA), carbohydrate antigen 15.3 (CA15.3), and carbohydrate antigen 27.29 (CA27.29) exhibited certain limitations. Poor sensitivity and specificity greatly limits the diagnostic accuracy of these markers. This study aims to identify potential tumor markers for breast cancer. At first, we analyzed genes expression in infiltrating lobular carcinoma, metaplastic carcinoma, and infiltrating ductal carcinoma of paired specimens (tumor and normal tissue) from breast cancer patients using microarray technology. We selected 371 overexpressed genes in all of the three cell type. In advanced breast cancer tissue, we detected four genes MMP13, CAMP, COL10A1 and FLJ25416 from 25 overexpressed genes which encoded secretion protein more specifically for breast cancer than other genes. After validation with 15 pairs of breast cancer tissue and paired to normal adjacent tissues by membrane array and quantitative RT-PCR, we found MMP13 was 100% overexpressed and confirmed to be a secreted protein by Western blot analysis of the cell culture medium. The expression level of MMP13 was also measured by immunohistochemical staining. We suggest that MMP13 is a highly overexpressed secretion protein in breast cancer tissue. It has potential to be a new tumor marker for breast cancer diagnosis.
在过去十年间,台湾地区乳腺癌的发病率逐年上升。乳腺癌是台湾女性中最常见的癌症,也是癌症相关死亡的第四大主要原因。乳腺癌早期不仅治疗选择范围更广,而且治疗成功率也高于晚期乳腺癌患者。肿瘤标志物检测是筛查乳腺癌最便捷的方法。然而,目前可用于乳腺癌检测的肿瘤标志物,包括癌胚抗原(CEA)、糖类抗原15.3(CA15.3)和糖类抗原27.29(CA27.29),都存在一定局限性。敏感性和特异性较差极大地限制了这些标志物的诊断准确性。本研究旨在寻找潜在的乳腺癌肿瘤标志物。首先,我们利用微阵列技术分析了乳腺癌患者配对标本(肿瘤组织和正常组织)中浸润性小叶癌、化生性癌和浸润性导管癌的基因表达。我们在所有这三种细胞类型中筛选出371个过表达基因。在晚期乳腺癌组织中,我们从25个过表达基因中检测到4个基因,即基质金属蛋白酶13(MMP13)、CAMP、10型胶原α1链(COL10A1)和FLJ25416,这些基因编码的分泌蛋白比其他基因更具乳腺癌特异性。通过膜阵列和定量逆转录-聚合酶链反应(RT-PCR)对15对乳腺癌组织及其配对的癌旁正常组织进行验证后,我们发现MMP13的过表达率为100%,并且通过对细胞培养基的蛋白质免疫印迹分析证实其为分泌蛋白。MMP13的表达水平也通过免疫组织化学染色进行了检测。我们认为MMP13是乳腺癌组织中高度过表达的分泌蛋白。它有潜力成为乳腺癌诊断的新型肿瘤标志物。