Zhang Lei, Yang Xiao, Zhong Lai-ping, Zhou Xiao-jian, Pan Hong-ya, Wei Kui-jie, Li Jiang, Chen Wan-tao, Zhang Zhi-yuan
Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
J Oral Pathol Med. 2009 Apr;38(4):362-70. doi: 10.1111/j.1600-0714.2008.00678.x. Epub 2008 Jul 31.
Previously, we established an in vitro cellular carcinogenesis model of oral squamous cell carcinoma (OSCC), including the human immortalized oral epithelia cells (HIOECs) and its derived cancerous HB96 cells. In this study, comparative proteomic analysis identified that Annexin A1 was one of the significantly down-regulated genes in the cancerous HB96 cells. To investigate Annexin A1 down-regulation and its potential usefulness as a molecular marker in OSCC, we further screened Annexin A1 expressions with a panel of OSCC lines, and clinical samples of cancerous and the paired adjacent normal tissues from primary OSCC patients. By Western blot analysis and real-time PCR, we showed that both Annexin A1 mRNA and protein expressions decreased in OSCC cell lines except in two cell lines for the mRNA levels. Immunohistochemistry and real-time PCR also showed that both Annexin A1 mRNA and protein expressions decreased in the cancerous tissues from OSCC patients compared with those in the paired adjacent non-malignant epithelia. More importantly, both Annexin A1 mRNA and protein expressions negatively correlated with the pathologic differentiation grades of cancerous tissues. The lower Annexin A1 mRNA or protein expressions correlated with the poorer pathologic differentiation grades. These results suggest that decreased expression of Annexin A1 contributes to the cancerous progression of OSCC, and Annexin A1 may be a potential biomarker for pathologic differentiation grade of OSCC.
此前，我们建立了一种口腔鳞状细胞癌（OSCC）的体外细胞癌变模型，包括人永生化口腔上皮细胞（HIOECs）及其衍生的癌性HB96细胞。在本研究中，比较蛋白质组学分析确定膜联蛋白A1是癌性HB96细胞中显著下调的基因之一。为了研究膜联蛋白A1的下调及其作为OSCC分子标志物的潜在用途，我们进一步用一组OSCC细胞系以及原发性OSCC患者的癌组织和配对的相邻正常组织的临床样本筛选了膜联蛋白A1的表达。通过蛋白质免疫印迹分析和实时定量PCR，我们发现除了两个细胞系的mRNA水平外，OSCC细胞系中膜联蛋白A1的mRNA和蛋白表达均降低。免疫组织化学和实时定量PCR还显示，与配对的相邻非恶性上皮相比，OSCC患者癌组织中膜联蛋白A1的mRNA和蛋白表达均降低。更重要的是，膜联蛋白A1的mRNA和蛋白表达均与癌组织的病理分化程度呈负相关。膜联蛋白A1的mRNA或蛋白表达越低，病理分化程度越差。这些结果表明，膜联蛋白A1表达降低促进了OSCC的癌变进程，膜联蛋白A1可能是OSCC病理分化程度的潜在生物标志物。
