Chou Chu-Chung, Chou Ming-Jen, Tzen Chin-Yuan
Department of Emergency Medicine, Changhua Christian Hospital, 135, Nanhsiao Street, Changhua 500, Taiwan.
Med Oncol. 2009;26(3):322-6. doi: 10.1007/s12032-008-9124-5. Epub 2008 Nov 15.
This study was aimed to test whether PIK3CA, BRAF and RAS are mutated in nasopharyngeal carcinomas (NPCs) and, if so, to further determine whether such mutations affect patients' survival. For this purpose, a total of 73 NPCs were subjected to mutational analyses for PIK3CA (exons 4, 7, 9, and 20), BRAF (codon 600), and RAS (codons 12, 13 and 61). Clinicopathological characteristics were correlated to the mutation data. Survival rates were compared with the log-rank test. The result showed that the mutation rate of PIK3CA in NPC (n = 73) was 9.6%, whereas both BRAF (n = 65) and RAS (n = 45) were wild type in every specimen with adequate DNA for analysis. PIK3CA mutation was slightly influenced by sex (P = 0.0418, Fisher's exact test), but had no significant relationship to other clinicopathological characteristics. Disease-specific survival was not significantly affected by PIK3CA mutations (P = 0.8825, log-rank test), albeit it was slightly better in younger patients (< or = 35 vs. >35 years of age) (P = 0.0477). These findings show that mutated PI3K may be involved in the NPC tumorigenesis but does not affect patient's prognosis, suggesting that PI3K is a potential target in NPC for targeted therapeutics using specific kinase inhibitors.
本研究旨在检测PIK3CA、BRAF和RAS在鼻咽癌(NPC)中是否发生突变,若发生突变,则进一步确定此类突变是否影响患者的生存。为此,对总共73例NPC进行了PIK3CA(第4、7、9和20外显子)、BRAF(第600密码子)和RAS(第12、13和61密码子)的突变分析。将临床病理特征与突变数据相关联。采用对数秩检验比较生存率。结果显示,NPC(n = 73)中PIK3CA的突变率为9.6%,而BRAF(n = 65)和RAS(n = 45)在每例有足够DNA用于分析的标本中均为野生型。PIK3CA突变受性别影响较小(P = 0.0418,Fisher精确检验),但与其他临床病理特征无显著关系。PIK3CA突变对疾病特异性生存无显著影响(P = 0.8825,对数秩检验),尽管在年轻患者(≤35岁与>35岁)中生存情况略好(P = 0.0477)。这些发现表明,突变的PI3K可能参与NPC的肿瘤发生,但不影响患者的预后,提示PI3K是NPC中使用特定激酶抑制剂进行靶向治疗的潜在靶点。