KRAS Mutation is Associated with Worse Prognosis in Stage III or High-risk Stage II Colon Cancer Patients Treated with Adjuvant FOLFOX
KRAS Mutation is Associated with Worse Prognosis in Stage III or High-risk Stage II Colon Cancer Patients Treated with Adjuvant FOLFOX
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DOI：
10.1245/s10434-014-3826-z
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发表时间：
2015-01-01
影响因子：
3.7
通讯作者：
Kim, Tae-You
中科院分区：
文献类型：
--
作者：
Lee, Dae-Won;Kim, Kyung Ju;Kim, Tae-You
尽管KRAS突变在接受抗EGFR治疗的IV期结直肠癌（CRC）患者中具有预测作用，但KRAS突变在II期或III期疾病中的预后影响存在争议。本研究的目的是评估KRAS和BRAF突变对接受辅助5-氟尿嘧啶/亚叶酸/奥沙利铂（FOLFOX）治疗的患者的预后影响。分析了接受根治性切除术后接受辅助FOLFOX的II期和III期CRC患者的KRAS外显子2和BRAF密码子600。比较437例患者的临床病理特征和无病生存期，其中388例有KRAS突变数据，433例有BRAF突变数据。KRAS突变（密码子12和13）和BRAF V600 E突变分别见于26.5%和3.7%的患者。与KRAS野生型患者相比，KRAS突变患者的DFS显著更差（3年DFS 79和92%，p = 0.006）。多变量分析显示KRAS突变是DFS的独立阴性预后因素（校正风险比2.30，95%置信区间1.23-4.32）。在KRAS突变的各种亚型中，G13 D（3年DFS 76%，p = 0.008）与DFS不良显著相关，而G12 D与预后无关（3年DFS 86%，p = 0.61）。BRAF突变与DFS无相关性，KRAS突变对辅助FOLFOX治疗的II期或III期CRC有不良预后影响。
Although KRAS mutation has a predictive role in stage IV colorectal cancer (CRC) patients treated with anti-EGFR therapy, there have been controversies in the prognostic impact of KRAS mutation in stage II or III disease. The purpose of this study was to assess the prognostic impact of KRAS and BRAF mutation in patients treated with adjuvant 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX).KRAS exon 2 and BRAF codon 600 were analyzed in patients with stage II and III CRC who underwent curative resection followed by adjuvant FOLFOX. Clinicopathologic features and disease-free survival (DFS) were compared.Among a total of 437 patients, mutational data of KRAS and BRAF were available in 388 and 433 patients, respectively. KRAS mutation (codon 12 and 13) and BRAF V600E mutation was found in 26.5 and 3.7 % of patients. DFS was significantly worse in the KRAS mutant patients compared to KRAS wild type patients (3-year DFS 79 and 92 %, p = 0.006). Multivariate analysis revealed KRAS mutation as an independent negative prognostic factor for DFS (adjusted hazard ratio 2.30, 95 % confidence interval 1.23-4.32). Among the various subtypes of KRAS mutation, G13D (3-year DFS 76 %, p = 0.008) was significantly associated with poor DFS, while G12D was not associated with prognosis (3-year DFS 86 %, p = 0.61). There was no association between BRAF mutation and DFS.KRAS mutation has an adverse prognostic impact on stage II or III CRC treated with adjuvant FOLFOX.