携带与未携带KIT基因557/558缺失突变胃肠道间质瘤患者术后无复发生存及影响因素分析

Postoperative recurrence-free survival and influencing factors of gastrointestinal stromal tumors patients with and without KIT gene 557/558 deletion mutations

  • 摘要:
    目的 探讨携带与未携带KIT基因外显子11密码子557/558缺失突变(简称557/558缺失突变)胃肠道间质瘤(GISTs)患者术后无复发生存情况及影响因素。
    方法 采用倾向评分匹配及回顾性队列研究方法。收集2006年1月至2022年12月江苏省苏北人民医院收治的337例行手术治疗GISTs患者的临床病理资料;男198例,女139例;年龄为(59±10)岁。337例原发性GISTs患者中,97例携带KIT基因557/558缺失突变,设为557/558缺失突变组;240例未携带KIT基因557/558缺失突变,设为非557/558缺失突变组。观察指标:(1)倾向评分匹配情况及匹配后两组患者临床病理特征比较。(2)随访及无复发生存情况。(3)患者无复发生存的影响因素分析。计数资料组间比较采用χ²检验。等级资料组间比较采用非参数秩和检验。采用Kaplan-Meier法计算生存率并绘制生存曲线,Log-rank检验进行生存分析。采用Cox比例风险模型进行单因素和多因素分析。倾向评分匹配按1∶1最近邻匹配法匹配,卡钳值为0.02。
    结果 (1)倾向评分匹配情况及匹配后两组患者临床病理特征比较。337例患者中,168例匹配成功,557/558缺失突变组和非557/558缺失突变组各84例。倾向评分匹配后,消除匹配前核分裂象计数、改良美国国立卫生研究院危险度分级、美国武装部队病理学研究所风险分级因素混杂偏倚,具有可比性。(2)随访及无复发生存情况。337例患者均获得随访,随访时间为35(2~120)个月,术后发生复发转移55例。倾向评分匹配后,557/558缺失突变组患者1、2、5年无复发生存率分别为96.34%95%可信区间(CI)为89.08%~98.80%、88.28%(95%CI为78.63%~93.74%)、70.54%(95%CI为55.26%~81.44%);非557/558缺失突变组患者1、2、5年无复发生存率分别为92.78%(95%CI为84.64%~96.69%)、87.44%(95%CI为77.86%~93.06%)、84.00%(95%CI为73.33%~90.67%);两组患者无复发生存情况比较,差异无统计学意义(χ2=2.291,P > 0.05)。(3)患者无复发生存的影响因素分析。倾向评分匹配前,多因素分析结果显示:肿瘤部位、肿瘤长径、核分裂象计数、基因突变分型均是GISTs患者术后无复发生存的独立影响因素(风险比=3.262、1.110、3.041、7.082、2.945,95%CI为1.874~5.680、1.039~1.186、1.681~5.503、3.304~15.180、1.681~5.158,P < 0.05)。
    结论 携带与未携带KIT基因557/558缺失突变GISTs患者术后无复发生存情况比较,差异无统计学意义;肿瘤部位、肿瘤长径、核分裂象计数、基因突变分型均是GISTs患者术后无复发生存的独立影响因素。

     

    Abstract:
    Objective To investigate the postoperative recurrence-free survival (RFS) and influencing factors of gastrointestinal stromal tumors (GISTs) patients with and without KIT gene exon 11 codon 557 and/or 558 deletion mutations (referred to as 557/558 deletion mutations).
    Methods The propensity score matching and retrospective cohort study was conducted. The clinico-pathological data of 337 patients with GISTs who underwent operation at Northern Jiangsu People′s Hospital from January 2006 to December 2022 were collected. There were 198 males and 139 females, aged (59±10)years. Of 337 patients with primary GISTs, 97 cases with KIT gene 557/558 deletion mutations were allocated into 557/558del group, and the rest 240 cases without KIT gene 557/558 deletion mutations were allocated into non-557/558del group. Observation indi-cators: (1) propen-sity score matching and comparison of clinicopathological data of patients between the two groups after matching; (2) follow-up and RFS; (3) analysis of influencing factors for RFS of patients. Compari-son of count data between groups was conducted using the chi-square test. Com-parison of ordinal data between groups was conducted using the non parametric rank sum test. Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Propensity score matching was done by the 1∶1 nearest neighbor matching method. The caliper value was set as 0.02.
    Results (1) Propensity score matching and comparison of clinicopatholo-gical data of patients between the two groups after matching. Of 337 patients, 168 cases were succe-ssfully matched, including 84 cases in the 557/558del group and 84 cases in the non-557/558del group.After propensity score matching, the confounding bias of mitotic index, modified National Institutes of Health risk classification, Armed Forces Institute of Pathology risk classifica-tion before matching were eliminated between the two groups, ensuring comparability. (2) Follow-up and RFS. All 337 patients were followed up for 35(range 2‒120)months. There were 55 cases of postoperative recurrence or metastasis. After propensity score matching, the 1-, 2-, and 5-year RFS rates in the 557/558 del group were 96.34% 95% confidence interval (CI) as 89.08%-98.80%, 88.28%(95%CI as 78.63%-93.74%), and 70.54%(95%CI as 55.26%-81.44%), respectively. For the non-557/558 del group, the corresponding rates were 92.78%(95%CI as 84.64%-96.69%), 87.44%(95%CI as 77.86%- 93.06%), and 84.00%(95%CI as 73.33%-90.67%). There was no significant difference in RFS between the two groups (χ2=2.291, P > 0.05).(3) Analysis of influencing factors for RFS of patients. Results of multivariate analysis showed that tumor location, tumor diameter, mitotic index, and muta-tion subtype were independent factors influencing postoperative RFS of GISTs patients before pro-pensity score matching (hazard ratio=3.262, 1.110, 3.041, 7.082, 2.945, 95%CI as 1.874-5.680, 1.039-1.186, 1.681-5.503, 3.304-15.180, 1.681-5.158, P < 0.05).
    Conclusions There is no significant difference in postoperative RFS of GISTs patients with and without KIT gene 557/558 deletion muta-tions. Tumor location, tumor diameter, mitotic index and mutation subtype are independent factors influencing postoperative RFS in GISTs patients.

     

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