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BRAF 突变是结直肠癌肝转移切除术的预后生物标志物。

BRAF mutation is a prognostic biomarker for colorectal liver metastasectomy.

机构信息

Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

出版信息

J Surg Oncol. 2012 Aug 1;106(2):123-9. doi: 10.1002/jso.23063. Epub 2012 Feb 13.

Abstract

BACKGROUND AND OBJECTIVES

In metastatic colorectal cancer, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) is a predictive biomarker for anti-epidermal growth factor receptor (EGFR) treatment and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) is a prognostic biomarker. We aimed to determine the impact of KRAS and BRAF mutation as determined from liver metastases specimens on overall survival (OS) in patients following colorectal liver metastasectomy.

METHODS

Liver metastases specimens (n = 292) obtained from patients after liver metastasectomy were used to determine the KRAS/BRAF genotype. Associations between clinicopathological parameters and KRAS/BRAF genotype were identified by univariate and multivariate analyses using the Cox proportional hazards model. The impact of KRAS/BRAF genotype on survival was analyzed using the Kaplan-Meier method.

RESULTS

The 5-year survival rate of the cohort was 55.8%. The KRAS and BRAF mutation rates were 38.0 and 2.1%, respectively. BRAF genotype, but not KRAS, was found to be an independent prognostic biomarker (HR = 5.181, P = 0.002) after adjustment for other significant confounding clinicopathological variates: Number of liver metastases (HR = 1.983, P = 0.009), concomitant extrahepatic disease (HR = 1.858, P = 0.014), and surgical margin (HR = 3.241, P < 0.001). BRAF genotype was an independent prognostic biomarker in patients with liver metastases only after metastasectomy (HR = 6.245, P < 0.003).

CONCLUSIONS

BRAF mutation is an independent prognostic biomarker for colorectal liver metastasectomy.

摘要

背景与目的

在转移性结直肠癌中,v-Ki-ras2 Kirsten 大鼠肉瘤病毒癌基因同源物(KRAS)是抗表皮生长因子受体(EGFR)治疗的预测生物标志物,而 V-raf 鼠肉瘤病毒癌基因同源物 B1(BRAF)是一种预后生物标志物。我们旨在确定从结直肠癌肝转移患者的肝转移标本中确定的 KRAS 和 BRAF 突变对结直肠癌肝转移切除术后患者总生存(OS)的影响。

方法

使用从肝转移切除术后患者获得的肝转移标本来确定 KRAS/BRAF 基因型。通过单变量和多变量分析使用 Cox 比例风险模型确定临床病理参数与 KRAS/BRAF 基因型之间的关联。使用 Kaplan-Meier 方法分析 KRAS/BRAF 基因型对生存的影响。

结果

该队列的 5 年生存率为 55.8%。KRAS 和 BRAF 突变率分别为 38.0%和 2.1%。调整其他显著混杂临床病理变量后,BRAF 基因型而非 KRAS 被发现是独立的预后生物标志物(HR=5.181,P=0.002):肝转移的数量(HR=1.983,P=0.009),同时存在肝外疾病(HR=1.858,P=0.014),和手术切缘(HR=3.241,P<0.001)。BRAF 基因型仅在肝转移切除术后是肝转移患者的独立预后生物标志物(HR=6.245,P<0.003)。

结论

BRAF 突变是结直肠癌肝转移切除术后的独立预后生物标志物。

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