Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Int J Clin Oncol. 2013 Dec;18(6):1042-8. doi: 10.1007/s10147-012-0501-x. Epub 2012 Nov 29.
Mutations of the KRAS or BRAF genes are now recognized as prognostic markers for colorectal cancer (CRC). They are also important predictive markers for resistance to the monoclonal antibodies that target the epidermal growth factor receptor.
In this retrospective study, KRAS and BRAF mutations were analyzed using a direct sequence method in 254 Japanese CRC patients, and the associations between KRAS or BRAF mutations and clinicopathological characteristics or outcome were evaluated.
KRAS and BRAF mutations were detected in 33.5 and 6.7 % of all patients, respectively. Consistent with previous reports, BRAF mutations were significantly correlated with the anatomical site of the tumor (P < 0.001), tumor grade (P = 0.001) and high frequency of microsatellite instability (P < 0.001). BRAF mutations were correlated with poor overall survival in the full patient cohort (P = 0.009). KRAS mutations were significantly correlated with poor recurrence-free survival (P = 0.03), particularly in patients with stage II CRC (P = 0.007). Cox regression analysis showed that KRAS mutations were a negative predictor of recurrence-free survival in patients with stage II CRC.
KRAS mutation status could be a novel biomarker for predicting disease recurrence in Japanese patients with stage II CRC.
KRAS 或 BRAF 基因突变现已被认为是结直肠癌（CRC）的预后标志物。它们也是针对表皮生长因子受体的单克隆抗体的耐药性的重要预测标志物。
在这项回顾性研究中，对 254 例日本 CRC 患者使用直接测序法分析了 KRAS 和 BRAF 基因突变，并评估了 KRAS 或 BRAF 基因突变与临床病理特征或结局之间的关系。
所有患者中分别检测到 33.5%和 6.7%的 KRAS 和 BRAF 基因突变。与先前的报告一致，BRAF 基因突变与肿瘤的解剖部位（P<0.001）、肿瘤分级（P=0.001）和高微卫星不稳定性频率（P<0.001）显著相关。BRAF 突变与全患者队列的总生存不良相关（P=0.009）。KRAS 突变与无复发生存不良显著相关（P=0.03），特别是在 II 期 CRC 患者中（P=0.007）。Cox 回归分析显示，KRAS 突变是 II 期 CRC 患者无复发生存的负面预测因子。
KRAS 突变状态可能是预测日本 II 期 CRC 患者疾病复发的新型生物标志物。
