Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway.
Clin Exp Metastasis. 2013 Oct;30(7):867-76. doi: 10.1007/s10585-013-9587-4. Epub 2013 May 15.
Metastatic melanoma is characterized by a poor response to chemotherapy. Furthermore, there is a lack of established predictive and prognostic markers. In this single institution study, we correlated mutation status and expression levels of BRAF and NRAS to dacarbazine (DTIC) treatment response as well as progression-free and overall survival in a cohort of 85 patients diagnosed with advanced melanoma. Neither BRAF nor NRAS mutation status correlated to treatment response. However, patients with tumors harboring NRAS mutations had a shorter overall survival (p < 0.001) compared to patients with tumors wild-type for NRAS. Patients having a clinical benefit (objective response or stable disease at 3 months) on DTIC therapy had lower BRAF and NRAS expression levels compared to patients progressing on therapy (p = 0.037 and 0.003, respectively). For BRAF expression, this association was stronger among patients with tumors wild-type for BRAF (p = 0.005). Further, low BRAF as well as NRAS expression levels were associated with a longer progression-free survival in the total population (p = 0.004 and <0.001, respectively). Contrasting low NRAS expression levels, which were associated with improved overall survival in the total population (p = 0.01), low BRAF levels were associated with improved overall survival only among patients with tumors wild-type for BRAF (p = 0.013). These findings indicate that BRAF and NRAS expression levels may influence responses to DTIC as well as prognosis in patients with advanced melanoma.
转移性黑色素瘤对化疗反应较差。此外，缺乏既定的预测和预后标志物。在这项单机构研究中，我们将 BRAF 和 NRAS 的突变状态和表达水平与达卡巴嗪（DTIC）治疗反应以及 85 名晚期黑色素瘤患者的无进展生存期和总生存期相关联。BRAF 或 NRAS 突变状态与治疗反应均无相关性。然而，携带 NRAS 突变的肿瘤患者的总生存期较短（p<0.001），与 NRAS 野生型肿瘤患者相比。在 DTIC 治疗中有临床获益（3 个月时客观缓解或疾病稳定）的患者与进展性疾病患者相比，BRAF 和 NRAS 的表达水平较低（p=0.037 和 0.003）。对于 BRAF 表达，在 BRAF 野生型肿瘤患者中这种相关性更强（p=0.005）。此外，在总人群中，低 BRAF 和 NRAS 表达水平与无进展生存期延长相关（p=0.004 和 <0.001）。与低 NRAS 表达水平相关的总生存期改善相反（p=0.01），在总人群中，低 BRAF 水平仅与 BRAF 野生型肿瘤患者的总生存期改善相关（p=0.013）。这些发现表明，BRAF 和 NRAS 表达水平可能影响晚期黑色素瘤患者对 DTIC 的反应和预后。
