Fendri Ali, Khabir Abdelmajid, Mnejja Wafa, Sellami-Boudawara Tahia, Daoud Jamel, Frikha Mounir, Ghorbel Abdelmonem, Gargouri Ali, Mokdad-Gargouri Raja
Laboratory of Cancer Genetic and Production of Recombinant Proteins, Route Sidi, Mansour Sfax, Sfax, Tunisia.
Cancer Sci. 2009 Nov;100(11):2034-9. doi: 10.1111/j.1349-7006.2009.01292.x. Epub 2009 Jul 21.
PI3Ks (phosphatidylinositol 3-kinases) are lipid kinases that regulate signalling pathways involved in cell proliferation, motility, and adhesion. Somatic mutations and amplification of the PIK3CA gene have been reported in various types of human cancers. However, little is known about the frequency and prognosis role of PIK3CA activation in nasopharyngeal carcinoma (NPC). This study was conducted with the aim to screen for PIK3CA mutations in the two hot spot regions (exons 9 and 20) and to investigate for the PIK3CA gene amplification combined with the expression analysis of the phosphorylated Akt (pAkt). We showed that among 88 specimens, none had mutation in the helical domain (exon 9) and only one (1.13%) had mutation in the kinase domain (exon 20). On the other hand, PIK3CA gene amplification was found in 21.6% of cases and was strongly associated with distant metastasis (P = 0.002), lymph node involvement (P = 0.032), and advanced tumor stage (P < 0.001). Moreover, patients with PIK3CA copy number gain have a significant reduced overall survival time (P log rank = 0.02). We concluded that PIK3CA gene amplification is frequent in NPC and occurs in the advanced stage of NPC. Moreover, our finding emphasizes the association of PIK3CA gene amplification with worse prognosis in nasopharyngeal carcinoma.
磷脂酰肌醇3激酶（PI3Ks）是一类脂质激酶，可调节参与细胞增殖、运动和黏附的信号通路。在各类人类癌症中均有PIK3CA基因的体细胞突变和扩增的报道。然而，关于PIK3CA激活在鼻咽癌（NPC）中的频率及预后作用却知之甚少。本研究旨在筛查两个热点区域（外显子9和20）的PIK3CA突变，并结合磷酸化Akt（pAkt）的表达分析来研究PIK3CA基因扩增情况。我们发现，在88个样本中，螺旋结构域（外显子9）均无突变，只有1个样本（1.13%）在激酶结构域（外显子20）有突变。另一方面，21.6%的病例中发现有PIK3CA基因扩增，且其与远处转移（P = 0.002）、淋巴结受累（P = 0.032）及肿瘤晚期（P < 0.001）密切相关。此外，PIK3CA拷贝数增加的患者总生存时间显著缩短（P对数秩检验 = 0.02）。我们得出结论，PIK3CA基因扩增在鼻咽癌中很常见，且发生于鼻咽癌晚期。此外，我们的研究结果强调了PIK3CA基因扩增与鼻咽癌预后较差之间的关联。
