BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer.
BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer.
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BRAF突变是晚期和复发性结直肠癌的强大预后因素。
DOI：
10.1038/bjc.2011.19
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发表时间：
2011-03-01
影响因子：
8.8
通讯作者：
Yatabe, Y.
中科院分区：
文献类型：
--
作者：
Yokota, T.;Ura, T.;Shibata, N.;Takahari, D.;Shitara, K.;Nomura, M.;Kondo, C.;Mizota, A.;Utsunomiya, S.;Muro, K.;Yatabe, Y.
KRAS和BRAF的激活突变被关注为抗EGFR治疗的结直肠癌（CRC）患者的潜在预后和预测生物标志物。本研究探讨了晚期和复发性结直肠癌患者的临床病理特征和KRAS/BRAF突变对预后的影响。通过cycleave PCR分析了接受全身化疗的晚期和复发性CRC患者（n=229）的KRAS/BRAF基因型。采用考克斯比例风险模型，通过单变量和多变量分析确定与生存相关的预后因素。KRAS和BRAF突变分别存在于34.5%和6.5%的患者中。BRAF突变的肿瘤更可能发生在结肠右侧，并且是低分化腺癌或粘液癌，以及腹膜转移。BRAF突变阳性和KRAS 13突变阳性患者的中位总生存期（OS）分别为11.0和27.7个月，显著差于野生型（wt）KRAS和BRAF患者（40.6个月）（BRAF; HR=4.25，P<0.001，KRAS 13; HR=2.03，P=0.024）。通过多变量考克斯回归分析校正显著特征后，BRAF突变与OS差相关（HR=4.23，P=0.019）。突变的BRAF的存在是晚期和复发性CRC的最有力的预后因素之一。KRAS 13突变显示晚期和复发性CRC患者OS较差的趋势。
Activating mutation of KRAS and BRAF are focused on as potential prognostic and predictive biomarkers in patients with colorectal cancer (CRC) treated with anti-EGFR therapies. This study investigated the clinicopathological features and prognostic impact of KRAS/BRAF mutation in advanced and recurrent CRC patients. Patients with advanced and recurrent CRC treated with systemic chemotherapy (n=229) were analysed for KRAS/BRAF genotypes by cycleave PCR. Prognostic factors associated with survival were identified by univariate and multivariate analyses using the Cox proportional hazards model. KRAS and BRAF mutations were present in 34.5% and 6.5% of patients, respectively. BRAF mutated tumours were more likely to develop on the right of the colon, and to be of the poorly differentiated adenocarcinoma or mucinous carcinoma, and peritoneal metastasis. The median overall survival (OS) for BRAF mutation-positive and KRAS 13 mutation-positive patients was 11.0 and 27.7 months, respectively, which was significantly worse than that for patients with wild-type (wt) KRAS and BRAF (40.6 months) (BRAF; HR=4.25, P<0.001, KRAS13; HR=2.03, P=0.024). After adjustment for significant features by multivariate Cox regression analysis, BRAF mutation was associated with poor OS (HR=4.23, P=0.019). Presence of mutated BRAF is one of the most powerful prognostic factors for advanced and recurrent CRC. The KRAS13 mutation showed a trend towards poor OS in patients with advanced and recurrent CRC.
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影响因子：
50.5
作者：
Farina-Sarasqueta, A.;van Lijnschoten, G.;van den Brule, A. J. C.
通讯作者：
van den Brule, A. J. C.
KRAS密码子61、146和BRAF突变预测KRAS密码子12和13野生型转移性结直肠癌中对西妥昔单抗和伊立替康的抗性。
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Rajagopalan, H;Bardelli, A;Velculescu, VE
通讯作者：
Velculescu, VE
影响因子：
8.8
作者：
Catalano, V.;Loupakis, F.;Graziano, F.;Torresi, U.;Bisonni, R.;Mari, D.;Fornaro, L.;Baldelli, A. M.;Giordani, P.;Rossi, D.;Alessandroni, P.;Giustini, L.;Silva, R. R.;Falcone, A.;D'Emidio, S.;Fedeli, S. L.
通讯作者：
Fedeli, S. L.
影响因子：
24.5
作者：
Ogino S;Nosho K;Kirkner GJ;Kawasaki T;Meyerhardt JA;Loda M;Giovannucci EL;Fuchs CS
通讯作者：
Fuchs CS