胃肠道间质瘤中伊马替尼耐药与 KIT 和 PDGFRA 基因突变状态的相关性：一项荟萃分析。

Correlation of imatinib resistance with the mutational status of KIT and PDGFRA genes in gastrointestinal stromal tumors: a meta-analysis.

机构信息

Department of Pathology, Korea University Ansan Hospital, Ansan, Republic of Korea; Email:

出版信息

J Gastrointestin Liver Dis. 2013 Dec;22(4):413-8.

DOI:

Abstract

Imatinib resistance is the most important clinical issue in patients with gastrointestinal stromal tumor (GIST). However, the association of imatinib resistance with the genetic characteristics of GIST has not been clearly defined. Our meta-analysis aimed to investigate the association between imatinib resistance and KIT and PDGFRA mutations in GIST. METHODS. We identified all relevant studies in PubMed and Embase. The effect sizes were calculated as prevalence or odds ratio (OR) with a random-effects model. RESULTS. We identified 10 eligible studies that included 1083 GIST cases. Total imatinib resistance was found in 35.5 % of PDGFRA-mutant tumors (OR = 2.9, P = 0.038), 33.7% of wild-type tumors (KIT and PDGFRA non-mutant tumors; OR = 2.8, P = 0.002), and 27.4% of KIT-mutant tumors (OR = 0.3, P = 0.001). Primary imatinib resistance was found in 50.0% of PDGFRA-mutant tumors (OR = 10.9, P = 0.031), 33.4% of wild-type tumors (OR = 5.9, P = 0.060), and 8.9% of KIT-mutant tumors (OR = 0.2, P = 0.025). KIT exon 9-mutant tumors showed primary resistance more frequently than exon 11-mutant and other tumors (OR = 7.6, P < 0.001). Regarding secondary resistance associated with KIT second-site mutations, the exon 17 mutation (54.5%) was most frequent, followed by exon 13 (38.3%) and 14 (13.4%) mutations. CONCLUSION. Our meta-analysis indicates that imatinib resistance is closely associated with KIT and PDGFRA genotypes in GIST. Thus, the mutational status of KIT and PDGFRA might predict response to imatinib in GIST patients.

摘要

伊马替尼耐药是胃肠道间质瘤（GIST）患者最重要的临床问题。然而，伊马替尼耐药与 GIST 遗传特征的关系尚未明确界定。我们的荟萃分析旨在探讨 GIST 中伊马替尼耐药与 KIT 和 PDGFRA 突变的关系。

方法。我们在 PubMed 和 Embase 中确定了所有相关研究。使用随机效应模型计算效应大小作为患病率或比值比（OR）。

结果。我们确定了 10 项符合条件的研究，共纳入 1083 例 GIST 病例。PDGFRA 突变肿瘤的总伊马替尼耐药率为 35.5%（OR=2.9，P=0.038），野生型肿瘤（KIT 和 PDGFRA 非突变肿瘤；OR=2.8，P=0.002）为 33.7%，KIT 突变肿瘤为 27.4%（OR=0.3，P=0.001）。PDGFRA 突变肿瘤的原发性伊马替尼耐药率为 50.0%（OR=10.9，P=0.031），野生型肿瘤为 33.4%（OR=5.9，P=0.060），KIT 突变肿瘤为 8.9%（OR=0.2，P=0.025）。KIT 外显子 9 突变肿瘤比外显子 11 突变和其他肿瘤更常出现原发性耐药（OR=7.6，P<0.001）。关于与 KIT 第二部位突变相关的继发性耐药，exon17 突变（54.5%）最常见，其次是 exon13（38.3%）和 exon14（13.4%）突变。

结论。我们的荟萃分析表明，伊马替尼耐药与 GIST 中的 KIT 和 PDGFRA 基因型密切相关。因此，KIT 和 PDGFRA 的突变状态可能预测 GIST 患者对伊马替尼的反应。