METHODS: Multicenter retrospective analysis was performed for CRC patients with curative resection. Genetic profiling was consisted of microsatellite instability (MSI) testing, RAS (K-ras, and N-ras), and BRAF (v-Raf murine sarcoma viral oncogene homolog B1) V600E mutation. Multivariate analyses were conducted using logistic regression for synchronicity, and Cox proportional hazard model with stage-adjusting for overall survival (OS) and disease-free survival (DFS).
RESULTS: It was identified synchronous (n = 36) and solitary (n = 579) CRC with similar base line characteristics. RAS mutation was associated to synchronous CRC with no relations of MSI and BRAF. During median follow up of 77.8 month, Kaplan-meier curves showed significant differences according to MSI-high for OS, and in RAS, and BRAF mutation for DFS, respectively. In multivariable analyses, RAS and BRAF mutation were independent factors (RAS, HR = 1.808, 95% CI = 1.18-2.77, p = 0.007; BRAF, HR = 2.417, 95% CI = 1.32-4.41, p = 0.004). Old age was independent factor for OS (HR = 3.626, 95% CI = 1.09-12.00, p = 0.035).
CONCLUSIONS: This study showed that oncologic outcomes might differ according to mutation burden characterized by RAS, BRAF, and MSI between synchronous CRC and solitary CRC. In addition, our systematic review highlighted a lack of data and much heterogeneity in genetic characteristics and survival outcomes of synchronous CRC relative to that of solitary CRC.
方法:对接受根治性切除的CRC患者进行多中心回顾性分析。遗传分析包括微卫星不稳定性(MSI)测试,RAS(K-ras,和N-ras),和BRAF(v-Raf鼠肉瘤病毒癌基因同源物B1)V600E突变。多变量分析使用逻辑回归进行同步性,和Cox比例风险模型,对总生存期(OS)和无病生存期(DFS)进行阶段调整。
结果:确定了具有相似基线特征的同步(n=36)和孤立(n=579)CRC。RAS突变与同步CRC相关,与MSI和BRAF无关。在77.8个月的中位随访期间,卡普兰-迈尔曲线根据操作系统的MSI-high显示出显著差异,在RAS中,DFS的BRAF突变,分别。在多变量分析中,RAS和BRAF突变是独立因素(RAS,HR=1.808,95%CI=1.18-2.77,p=0.007;BRAF,HR=2.417,95%CI=1.32-4.41,p=0.004)。高龄是OS的独立影响因素(HR=3.626,95%CI=1.09~12.00,p=0.035)。
结论:这项研究表明,肿瘤结局可能因RAS的突变负荷而有所不同,BRAF,以及同步CRC和单独CRC之间的MSI。此外,我们的系统综述强调了与单独CRC相比,同步CRC的数据缺乏和遗传特征和生存结局的异质性.