Specific mutations in KRAS codon 12 are associated with worse overall survival in patients with advanced and recurrent colorectal cancer.
Specific mutations in KRAS codon 12 are associated with worse overall survival in patients with advanced and recurrent colorectal cancer.
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DOI：
10.1038/bjc.2017.37
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发表时间：
2017-03-28
影响因子：
8.8
通讯作者：
Malik HZ
中科院分区：
文献类型：
--
作者：
Jones RP;Sutton PA;Evans JP;Clifford R;McAvoy A;Lewis J;Rousseau A;Mountford R;McWhirter D;Malik HZ
KRAS的激活突变已被认为是潜在的预测和预后的生物标志物。然而，特定的点突变对预后的影响仍然不太清楚。这项研究评估了特定的KRAS突变对结直肠癌患者生存的预后影响。对2010至2015年间英国癌症网络中的晚期和复发性结直肠癌患者进行KRAS分型的回顾。我们评估了KRAS基因对392名患者的影响。突变的KRAS在42.9%的肿瘤中被检测到。KRAS突变在中分化肿瘤中比在高分化肿瘤中更为常见。多因素分析显示，原发肿瘤T分期(HR2.77(1.54~4.98)，P=0.001)、N分期(HR1.51(1.01~2.26)，P=0.04)、根治性手术治疗(HR0.51(0.34~0.76)，P=0.001)、肿瘤分级(HR0.44(0.30~0.65)，P=0.001)和KRAS突变(1.54(1.23~2.12)，P=0.005)均是影响预后的因素。KRAS密码子12突变患者的总生存率较低(HR1.76(95%CI1.27~2.43)，P=0.001)。在5个最常见的密码子12突变中，只有p.G12C(HR 2.21(1.15-4.25)，P=0.01)和p.G12V(HR 1.69(1.08-2.62)，P=0.02)预测总体生存。对于结直肠癌患者，第12密码子的p.G12C和p.G12V突变独立地与诊断后较差的总体存活率相关。
Activating mutations in KRAS have been suggested as potential predictive and prognostic biomarkers. However, the prognostic impact of specific point mutations remains less clear. This study assessed the prognostic impact of specific KRAS mutations on survival for patients with colorectal cancer. Retrospective review of patients KRAS typed for advanced and recurrent colorectal cancer between 2010 and 2015 in a UK Cancer Network. We evaluated the impact of KRAS genotype in 392 patients. Mutated KRAS was detected in 42.9% of tumours. KRAS mutations were more common in moderate vs well-differentiated tumours. On multivariate analysis, primary tumour T stage (HR 2.77 (1.54–4.98), P=0.001), N stage (HR 1.51 (1.01–2.26), P=0.04), curative intent surgery (HR 0.51 (0.34–0.76), P=0.001), tumour grade (HR 0.44 (0.30–0.65), P=0.001) and KRAS mutation (1.54 (1.23–2.12), P=0.005) were all predictive of overall survival. Patients with KRAS codon 12 mutations had worse overall survival (HR 1.76 (95% CI 1.27–2.43), P=0.001). Among the five most common codon 12 mutations, only p.G12C (HR 2.21 (1.15–4.25), P=0.01) and p.G12V (HR 1.69 (1.08–2.62), P=0.02) were predictive of overall survival. For patients with colorectal cancer, p.G12C and p.G12V mutations in codon 12 were independently associated with worse overall survival after diagnosis.