Houali Karim, Wang Xiaohui, Shimizu Yuko, Djennaoui Djamel, Nicholls John, Fiorini Sylvie, Bouguermouh Abdelmadjid, Ooka Tadamasa
Laboratoire de Virologie Moléculaire, UMR5537, Centre National de la Recherche Scientifique, Faculté de Médecine Laennec, Université Lyon-1, Lyon Cedex, France.
Clin Cancer Res. 2007 Sep 1;13(17):4993-5000. doi: 10.1158/1078-0432.CCR-06-2945.
EBV has been associated with nasopharyngeal carcinomas (NPC). In North Africa, the incidence is bimodal-the first peak occurring at approximately 20 years of age and the second peak occurring at approximately 50 years. Standard diagnostic tests based on immunofluorescence using anti-IgA EBV have shown that young North African patients have a negative serology compared with older patients. We are interested in two EBV-encoded oncoproteins, LMP1 and BARF1, which have thus far not been studied in terms of their potential as diagnostic markers for NPC. These two viral oncoproteins have been detected in cell culture media, so we tested whether they could be detected in the serum and saliva of patients with NPC.
LMP1 and BARF1 proteins were analyzed in the sera and saliva of young patients and adult patients with NPC from North Africa and China. We then examined whether the secreted proteins had biological activity by analyzing their mitogenic activity.
Both LMP1 and BARF1 were present in the serum and saliva from North African and Chinese patients with NPC. All young North African patients secreted both proteins, whereas 62% and 100% of adult patients secreted LMP1 and BARF1, respectively. From animal studies, the secreted LMP1 was associated with exosome-like vesicles. These secreted EBV oncoproteins showed a powerful mitogenic activity in B cells.
Both proteins will be a good diagnostic marker for NPC whereas BARF1 is a particularly promising marker for all ages of patients with NPC. Their mitogenic activity suggests their implication in the oncogenic development of NPC.
EB病毒与鼻咽癌(NPC)有关。在北非,发病率呈双峰模式——第一个高峰出现在大约20岁,第二个高峰出现在大约50岁。基于使用抗IgA EB病毒的免疫荧光的标准诊断测试表明,与老年患者相比,年轻的北非患者血清学呈阴性。我们对两种EB病毒编码的癌蛋白LMP1和BARF1感兴趣,到目前为止,尚未就它们作为鼻咽癌诊断标志物的潜力进行研究。这两种病毒癌蛋白已在细胞培养基中被检测到,因此我们测试了它们是否能在鼻咽癌患者的血清和唾液中被检测到。
对来自北非和中国的年轻鼻咽癌患者及成年鼻咽癌患者的血清和唾液中的LMP1和BARF1蛋白进行分析。然后,我们通过分析它们的促有丝分裂活性来检查分泌的蛋白是否具有生物活性。
LMP1和BARF1均存在于北非和中国鼻咽癌患者的血清和唾液中。所有年轻的北非患者都分泌这两种蛋白,而成年患者中分别有62%和100%分泌LMP1和BARF1。从动物研究来看,分泌的LMP1与外泌体样囊泡有关。这些分泌的EB病毒癌蛋白在B细胞中显示出强大的促有丝分裂活性。
这两种蛋白都将是鼻咽癌的良好诊断标志物,而BARF1对所有年龄段的鼻咽癌患者来说是一个特别有前景的标志物。它们的促有丝分裂活性表明它们与鼻咽癌的致癌发展有关。