胃的胃肠间质瘤患者基因突变状态及预后分析

Analysis of gene mutation status and prognosis of patients with gastric gastrointestinal stromal tumor

目的:分析胃的胃肠间质瘤(gastrointestinal stromal tumor,GIST)患者基因突变状态,探究不同基因突变类型对患者预后的影响。方法:回顾性分析华中科技大学同济医学院附属协和医院2012年1月—2021年6月术后行基因检测的胃GIST患者的临床病理资料。采用Kaplan-Meier法绘制生存曲线并计算存活率。采用COX比例风险模型进行单因素和多因素预后分析。结果:共纳入286例胃GIST患者,其中男性152例、女性134例;中位年龄为57岁(范围:21~85岁)。KIT基因第11、9、13、17号外显子突变比例分别为78.0%(223/286)、2.4%(7/286)、1.4%(4/286)、1.0%(3/286),血小板源性生长因子受体α(platelet-derived growth factor receptor alpha,PDGFRA)基因第18、12号外显子突变比例分别为10.1%(29/286)和0.7%(2/286),野生型胃GIST比例为6.3%(18/286)。KIT第11号外显子突变患者中缺失、置换、插入、重复及混合突变的比例分别为40.4%(90/223)、29.1%(65/223)、5.8%(13/223)、5.8%(13/223)和18.8%(42/223)。生存分析显示,KIT外显子11缺失突变(P<0.001)和混合突变(P=0.004)患者的预后较其他突变类型的更差。中危非KIT外显子11缺失或混合突变患者的预后优于中危KIT外显子11缺失或混合突变患者(P=0.006)。中危KIT外显子11缺失或混合突变患者的预后与高危患者相近(P=0.644)。多因素COX分析显示,危险度分级为高危(风险比:4.384,95%置信区间:1.668~11.519;P=0.003)、KIT外显子11缺失或混合突变(风险比:6.445,95%置信区间:1.837~22.607;P=0.004)以及术后未行辅助治疗(风险比:3.492,95%置信区间:1.442~8.458;P=0.006)是影响胃GIST患者无复发生存期的独立危险因素。结论:KIT外显子11缺失突变或混合突变与胃GIST患者的不良预后相关。KIT外显子11缺失突变或混合突变的中危胃GIST患者的预后与高危胃GIST患者的相近。

Objective:To analyze the gene mutation status of patients with gastric gastrointestinal stromal tumor(GIST)and explore the effect of different gene mutation types on the prognosis of patients.Methods:The clinicopathological data of patients with gastric GIST who underwent gene testing in Union Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2012 to June 2021 were analyzed retrospectively.Kaplan-Meier method was used to plot the survival curve and calculate the survival rate.Univariate and multivariate prognostic analyses were performed by COX proportional risk model.Results:A total of 286 patients with gastric GIST were enrolled,including 152 males and 134 females.The median age of patients was 57(21-85)years.The proportions of KIT gene mutations in exon 11,9,13 and 17 were 78.0%(223/286),2.4%(7/286),1.4%(4/286)and 1.0%(3/286),respectively.The proportion of platelet derived growth factor receptor alpha(PDGFRA)gene mutations in exon 18 and 12 were 10.1%(29/286)and 0.7%(2/286),respectively.The proportion of wild-type gastric GIST was 6.3%(18/286).The proportions of deletion,substitution,insertion,duplication and mixed mutation of KIT 11 exon were 40.4%(90/223),29.1%(65/223),5.8%(13/223),5.8%(13/223)and 18.8%(42/223),respectively.Survival analysis showed that the prognosis of patients with KIT exon 11 deletion mutations(P<0.001)and mixed mutations(P=0.004)were worse than other mutation types.Patients in intermediate-risk with non-KIT exon 11 deletion/mixed mutation had better prognosis than those with KIT exon 11 deletion/mixed mutation(P=0.006).The prognosis of patients in intermediate-risk with KIT exon 11 deletion/mixed mutation was similar to high-risk patients(P=0.644).Multivariate COX analysis showed that patients with high-risk grade(hazard ratio:4.384,95%confidence interval:1.668-11.519,P=0.003),KIT exon 11 deletion/mixed mutation(hazard ratio:6.445,95%confidence interval:1.837-22.607,P=0.004)and no postoperative adjuvant treatment(hazard ratio:3.492,95%confidence interval:1.442-8.458,P=0.006)were independent risk factors for recurrence free survival of gastric GIST.Conclusion:KIT exon 11 deletion mutation or mixed mutation are associated with poor prognosis in patients with gastric GIST.Patients in gastric GIST of intermediate-risk with KIT exon 11 deletion mutations or mixed mutations have a similar prognosis to patients in gastric GIST of high-risk.