背景:基因改变对同步结直肠癌(CRC)的肿瘤学影响仍不清楚。这项研究旨在根据同步和单独CRC之间的遗传改变比较肿瘤学相关性。
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.
BACKGROUND: Oncologic impact of genetic alteration across synchronous colorectal cancer (CRC) still remains unclear. This
study aimed to compare the oncologic relevance according to genetic alteration between synchronous and solitary CRC with performing systematic review.
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.