Shi Yan, Chen Li, Li Jie, Lv Ya-Li, Sun Qiong, Wang Ling-Xiong, Jiao Shun-Chang
Department of Medical Oncology, General Hospital of CPLA, FuXing Road No. 28, Beijing 100853, China.
Tumour Biol. 2011 Apr;32(2):381-90. doi: 10.1007/s13277-010-0131-8. Epub 2010 Nov 18.
Ras/ERK and PI3K/Akt pathways are reported to play a prognostic role and contribute to drug resistance in many cancers. The objective of this study was to explore associations between the expression levels of several molecules in Ras/ERK and PI3K/Akt pathways and their clinical significance in predicting the effectiveness of postoperative adjuvant chemotherapy in patients with non-small cell lung cancer (NSCLC). The expressions of K-ras, Raf-1, ERK1/2, phosphorylated ERK1/2 (pERK1/2), Akt-1, phosphorylated Akt-1 (pAkt-1), and Bcl-2 were detected by immunohistochemistry in tumor specimens from 144 NSCLC patients. The correlations between the expression levels of these molecules and the clinicopathological characteristics were analyzed. Patient survival was analyzed by Kaplan-Meier method, log-rank test, and Cox regression. The positive expression rates of K-ras, Raf-1, ERK1/2, pERK1/2, Akt-1, pAkt-1, and Bcl-2 were 21.5%, 41.7%, 59.7%, 27.1%, 50.7%, 36.1%, and 30.6%, respectively. Univariate analysis showed that patients with pERK1/2-positive (P = 0.01), Bcl-2-positive (P = 0.023), or pAkt-1 negative (P = 0.021) had significantly better recurrence-free survival (RFS) than those with pERK1/2-negative, Bcl-2-negative, or pAkt-1-positive. Multivariate analysis showed that earlier stage (P ≤ 0.001), non-adenocarcinoma (P ≤ 0.001), pERK1/2-positive (P ≤ 0.001), and pAkt-1-negative (P = 0.016) were independent prognostic factors for a better RFS in NSCLC. pERK1/2-positive and pAkt-1-negative proved to contribute to a better RFS in postoperative NSCLC patients who received adjuvant chemotherapy after taking the stage and histological subtype into account. pERK1/2 and pAkt-1 could be considered as new independent prognostic biomarkers for predicting RFS and selecting patients who are more likely to benefit from postoperative adjuvant chemotherapy.
据报道，Ras/ERK和PI3K/Akt信号通路在许多癌症中发挥着预后作用并导致耐药性。本研究的目的是探讨Ras/ERK和PI3K/Akt信号通路中几种分子的表达水平与它们在预测非小细胞肺癌（NSCLC）患者术后辅助化疗疗效方面的临床意义之间的关联。通过免疫组织化学检测了144例NSCLC患者肿瘤标本中K-ras、Raf-1、ERK1/2、磷酸化ERK1/2（pERK1/2）、Akt-1、磷酸化Akt-1（pAkt-1）和Bcl-2的表达。分析了这些分子表达水平与临床病理特征之间的相关性。采用Kaplan-Meier法、对数秩检验和Cox回归分析患者生存率。K-ras、Raf-1、ERK1/2、pERK1/2、Akt-1、pAkt-1和Bcl-2的阳性表达率分别为21.5%、41.7%、59.7%、27.1%、50.7%、36.1%和30.6%。单因素分析显示，pERK1/2阳性（P = 0.01）、Bcl-2阳性（P = 0.023）或pAkt-1阴性（P = 0.021）的患者无复发生存期（RFS）明显优于pERK1/2阴性、Bcl-2阴性或pAkt-1阳性的患者。多因素分析显示，早期（P≤0.001）、非腺癌（P≤0.001）、pERK1/2阳性（P≤0.001）和pAkt-1阴性（P = 0.016）是NSCLC患者RFS较好的独立预后因素。在考虑分期和组织学亚型后，pERK1/2阳性和pAkt-1阴性被证明有助于接受辅助化疗的术后NSCLC患者获得更好的RFS。pERK1/2和pAkt-1可被视为预测RFS和选择更可能从术后辅助化疗中获益的患者的新的独立预后生物标志物。
