PIK3CA amplification is predictive of poor prognosis in Tunisian patients with nasopharyngeal carcinoma
PIK3CA amplification is predictive of poor prognosis in Tunisian patients with nasopharyngeal carcinoma
复制标题
DOI：
10.1111/j.1349-7006.2009.01292.x
复制
发表时间：
2009-11-01
期刊：
影响因子：
5.7
通讯作者：
Mokdad-Gargouri, Raja
中科院分区：
文献类型：
--
作者：
Fendri, Ali;Khabir, Abdelmajid;Mokdad-Gargouri, Raja
PI 3 K（磷脂酰肌醇3-激酶）是调节参与细胞增殖、运动和粘附的信号传导途径的脂质激酶。PIK 3CA基因的体细胞突变和扩增已在各种类型的人类癌症中报道。然而，PIK 3CA激活在鼻咽癌（NPC）中的频率和预后作用知之甚少。本研究的目的是筛查PIK 3CA两个热点区域（外显子9和20）的突变，并结合磷酸化Akt（pAkt）的表达分析来研究PIK 3CA基因的扩增。我们发现，在88例标本中，没有螺旋结构域（外显子9）的突变，只有一个（1.13%）的激酶结构域（外显子20）的突变。另一方面，PIK 3CA基因扩增在21.6%的病例中被发现，并且与远处转移（P= 0.002）、淋巴结受累（P= 0.032）和晚期肿瘤分期（P<0.001）密切相关。 此外，PIK 3CA拷贝数增加的患者总生存时间显著缩短（P log rank = 0.02）。 结论：PIK 3CA基因扩增在鼻咽癌中较常见，且发生于鼻咽癌的晚期。此外，我们的发现强调了PIK 3CA基因扩增与鼻咽癌预后不良的关系。（Cancer Sci2009）; 00：000-000）
PI3Ks (phosphatidylinositol 3‐kinases) are lipid kinases that regulate signalling pathways involved in cell proliferation, motility, and adhesion. Somatic mutations and amplification of thePIK3CAgene have been reported in various types of human cancers. However, little is known about the frequency and prognosis role ofPIK3CAactivation in nasopharyngeal carcinoma (NPC). This study was conducted with the aim to screen forPIK3CAmutations in the two hot spot regions (exons 9 and 20) and to investigate for thePIK3CAgene 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,PIK3CAgene 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 withPIK3CAcopy number gain have a significant reduced overall survival time (P log rank = 0.02). We concluded thatPIK3CAgene amplification is frequent in NPC and occurs in the advanced stage of NPC. Moreover, our finding emphasizes the association ofPIK3CAgene amplification with worse prognosis in nasopharyngeal carcinoma. (Cancer Sci2009); 00: 000–000)