Department of Surgery, Hallym Sacred Heart Hospital, Hallym University College of Medicine, Anyang Si, Republic of Korea.
Department of Surgery, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea.
BMC Gastroenterol. 2023 Sep 4;23(1):297. doi: 10.1186/s12876-023-02937-7.
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.
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).
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).
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.
遗传改变对结直肠癌（CRC）同步性的影响尚不清楚。本研究旨在通过系统回顾，比较具有明确治疗性切除的同步性和孤立性 CRC 中基于遗传改变的肿瘤相关性。
对具有明确治疗性切除的 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）检测、RAS（K-ras 和 N-ras）和 BRAF（v-Raf 鼠肉瘤病毒致癌基因同源物 B1）V600E 突变。使用逻辑回归进行同步性的多变量分析，使用具有分期调整的 Cox 比例风险模型进行总生存（OS）和无病生存（DFS）的多变量分析。
确定了具有相似基线特征的同步性（n=36）和孤立性（n=579）CRC。RAS 突变与同步性 CRC 相关，而与 MSI 和 BRAF 无关。在 77.8 个月的中位随访期间，根据 MSI-高，Kaplan-Meier 曲线显示 OS 存在显著差异，而在 RAS 和 BRAF 突变中，DFS 分别存在显著差异。在多变量分析中，RAS 和 BRAF 突变是独立的因素（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）。老年是 OS 的独立因素（HR=3.626，95%CI=1.09-12.00，p=0.035）。
本研究表明，RAS、BRAF 和 MSI 所代表的突变负担可能会导致同步性 CRC 和孤立性 CRC 的肿瘤结局不同。此外，我们的系统回顾强调，与孤立性 CRC 相比，同步性 CRC 的遗传特征和生存结果的数据缺乏且存在很大的异质性。
