Department of Radiation Oncology, The First People's Hospital of Xinyi, Xinyi, Jiangsu 221400, P.R. China.
Department of Radiation Oncology, The Affiliated Jiangsu Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
Oncol Rep. 2018 Apr;39(4):1966-1974. doi: 10.3892/or.2018.6277. Epub 2018 Feb 22.
Raf-1 proto-oncogene, serine/threonine kinase (Raf1) acts as a part of the RAS/RAF/MEK/ERK signaling pathway and regulates cell migration, apoptosis and differentiation. However, few studies are available on the expression and clinical significance of Raf1 in non‑small cell lung cancer (NSCLC). This study investigated the clinical value and prognostic significance of Raf1 in NSCLC patients, following radiotherapy. We evaluated the Raf1 expression using immunohistochemical analyses of samples from 110 NSCLC patients who received radiotherapy. The association between Raf1 expression and clinicopathological variables was also analyzed. The multivariate Cox proportional hazard model was used to determine the prognostic value of Raf1 in regards to progression and 3‑year survival. Significant associations between Raf1 expression and invasion and metastasis capability in lung cancer A549 and H1299 cell lines were identified. Results showed that 44.5% (49/110) of the NSCLC patient specimens demonstrated Raf1 expression, which was found to be positively correlated with lymph node metastasis (P=0.014), T stage (P=0.038) and poor histological differentiation (P=0.029). Later progression was observed in patients with negative or low Raf1 expression than in patients with high Raf1 expression (P=0.002). The multivariate analysis indicated that Raf1 is an independent prognostic factor for time to progression (TTP) (HR, 1.94; 95% CI, 1.16‑3.25; P=0.01). A high Raf1 expression was found to result in a poor 3‑year overall survival (OS)(HR, 1.64; 95% CI, 0.98‑2.75; P=0.06). Raf1 overexpression was correlated with early progression in NSCLC. Raf1 may serve as a novel prognostic factor and potential target for improving the long‑term outcome of NSCLC patients.
Raf-1 原癌基因,丝氨酸/苏氨酸激酶(Raf1)作为 RAS/RAF/MEK/ERK 信号通路的一部分,调节细胞迁移、凋亡和分化。然而,关于 Raf1 在非小细胞肺癌(NSCLC)中的表达和临床意义的研究较少。本研究探讨了 Raf1 在接受放疗的 NSCLC 患者中的临床价值和预后意义。我们使用免疫组织化学分析了 110 例接受放疗的 NSCLC 患者的样本,评估了 Raf1 的表达。还分析了 Raf1 表达与临床病理变量之间的关系。多变量 Cox 比例风险模型用于确定 Raf1 在进展和 3 年生存率方面的预后价值。在肺癌 A549 和 H1299 细胞系中发现 Raf1 表达与侵袭和转移能力之间存在显著相关性。结果显示,44.5%(49/110)的 NSCLC 患者标本表达 Raf1,其与淋巴结转移(P=0.014)、T 分期(P=0.038)和组织学分化不良(P=0.029)呈正相关。与 Raf1 低表达或阴性表达的患者相比,Raf1 高表达的患者后期进展更明显(P=0.002)。多变量分析表明,Raf1 是进展时间(TTP)的独立预后因素(HR,1.94;95%CI,1.16-3.25;P=0.01)。Raf1 高表达与 NSCLC 患者 3 年总生存率(OS)较差相关(HR,1.64;95%CI,0.98-2.75;P=0.06)。Raf1 过表达与 NSCLC 的早期进展相关。Raf1 可能成为改善 NSCLC 患者长期预后的新型预后因素和潜在靶点。