c-kit基因突变对胃肠道间质瘤预后影响的荟萃分析

Effect of c-kit mutation on the prognosis of gastrointestinal stromal tumors： a meta-analysis

目的探讨c-kil基因突变对胃肠道间质瘤（GIST）预后的影响。方法通过电子检索PubMed、MedLine数据库，对1999年1月至2008年8月有关c—kit基因突变对GIST预后影响相关病例对照研究资料，用RevMan5．0．15软件进行荟萃分析。结果共纳入文献16篇，共计患者1751例。其中与细胞病理学相关统计显示c-kit基因野生型与突变型在有丝分裂计数〉5／50HPF（高倍视野）的病例发生率上差异无统计学意义（P=0．710）；与术后复发转移发生率相关统计显示，c—kit基因突变型术后复发转移的发生率显著高于野生型者（P=0．010）；与伊马替尼疗效相关统计显示，c—kit基因突变型患者伊马替尼治疗缓解率显著高于野生型（P=0．009），而伊马替尼耐药率较低（P=0．000）。亚组分析发现，外显子11突变型的患者伊马替尼治疗缓解率显著高于野生型和外显子9突变型者（P均〈0．05），而伊马替尼耐药率较低（P均〈0．05）。c—kit基因二次突变与伊马替尼获得性耐药相关研究发现，二次突变区域集中在外显子13、14和17，部分为混合型突变。结论c—kit基因突变与GIST术后复发转移的发生有着密切关系，c—kit基因突变可能会影响伊马替尼的疗效，而二次突变的发生可能是GIST产生耐药的主要原因之一。

Objective To investigate the effect of c-kit mutation on the prognosis of gastrointestinal stromal tumors. Methods A search of studies in PubMed and MedLine （from 1999 to 2008） was performed to assess the effect of c-kit mutation on the prognosis of gastrointestinal stromal tumors. The articles were retrieved with the entries of ＂gastrointestinal stromal tumors＂ ,＂ imatinib＂ ,＂ c-kit＂ and ＂mutation＂. A meta- analysis was performed to assess the data included. Results A total of 15 articles were collected in this analysis. No significant differences was found in incidence of mitoses （ 〉 5/50 HPF） between the patients with wild type c-kit （wild type group ） and the ones with mutated c-kit （mutation group） （P = 0. 710 ）; tumor recurrence and metastasis rate after surgery was significant higher in the mutation group than that in wild type group （P = 0. 010） ; as for imatinib response with different c-kit mutation types, the results showed the incidence of clinical response（ complete response ＋ partial response） was significantly higher in mutation group than that in wild type group （P = 0. 009 ） , but the imatinib resistance rate was lower in mutation group （ P = 0. 000 ） ; three studies provided data for imatinib resistance with c-kit second mutations, the results showed the second mutations mainly focus on exon 13, 14, 17. Conclusions C-kit mutation is related closely with the incidence of recurrence and metastasis in GIST after surgery. The mutations of e-kit influences the therapeutic effects of imatinib.