Coelho Ana L, Araújo António, Gomes Mónica, Catarino Raquel, Marques Agostinho, Medeiros Rui
Molecular Oncology Group, Portuguese Institute of Oncology Porto, Porto, Portugal ; Faculty of Medicine, University of Porto, Porto, Portugal.
Molecular Oncology Group, Portuguese Institute of Oncology Porto, Porto, Portugal ; Medical Oncology Department, Centro Hospitalar de Entre o Douro e Vouga, Santa Maria da Feira, Portugal ; Abel Salazar Institute for the Biomedical Sciences, University of Porto, Porto, Portugal.
PLoS One. 2014 Feb 28;9(2):e90009. doi: 10.1371/journal.pone.0090009. eCollection 2014.
Non-small cell lung cancer (NSCLC) is the most common cancer and the leading cause of death from cancer worldwide. Antiangiogenic strategies directed towards tumor stroma are becoming gold standard in NSCLC treatment and researchers have been searching for biomarkers to identify patients for whom therapy with antiangiogenic inhibitors may be most beneficial and the importance of these as prognostic factors in NSCLC. The purpose of this study was to evaluate the prognostic value of circulating Ang-2 mRNA levels prior to treatment in NSCLC patients. The mRNA levels were determined by quantitative real-time PCR in the peripheral blood of 92 NSCLC patients. Our results demonstrate that patients with high circulating Ang-2 mRNA levels have diminished overall survival when compared to those with low mRNA levels (20.3 months vs 34.3 months, respectively; Log Rank Test, p = 0.016), when considering all NSCLC stages and this difference is even bigger when considering only patients with stage IV (15.9 months vs 31.3 months, respectively; Log Rank Test, p = 0.036). Moreover, circulating Ang-2 mRNA levels independently determine overall survival, and the concordance (c) index analysis showed that the definition of a nomogram that contains information regarding tumor stage, patients' smoking status and circulating Ang-2 mRNA levels present an increased capacity to predict overall survival in NSCLC patients (c-index 0.798). These results suggest that this nomogram could serve as a unique and practical tool to determine prognosis in NSCLC, not relying on the availability of adequate surgical or biopsy specimens of NSCLC. Attending to our results, the circulating Ang-2 mRNA levels should also be included in the design of preclinical studies and clinical trials involving antiangiogenic drugs targeting Ang-2, to guide adequate patient stratification and dose selection and increasing the likelihood of benefit to a level that is acceptable to patients and clinicians.
非小细胞肺癌（NSCLC）是全球最常见的癌症，也是癌症死亡的主要原因。针对肿瘤基质的抗血管生成策略正成为NSCLC治疗的金标准，研究人员一直在寻找生物标志物，以确定使用抗血管生成抑制剂治疗可能最有益的患者，以及这些标志物作为NSCLC预后因素的重要性。本研究的目的是评估NSCLC患者治疗前循环Ang-2 mRNA水平的预后价值。通过定量实时PCR测定了92例NSCLC患者外周血中的mRNA水平。我们的结果表明，与低mRNA水平的患者相比，循环Ang-2 mRNA水平高的患者总生存期缩短（分别为20.3个月和34.3个月；对数秩检验，p = 0.016），在考虑所有NSCLC分期时是这样，而仅考虑IV期患者时这种差异更大（分别为15.9个月和31.3个月；对数秩检验，p = 0.036）。此外，循环Ang-2 mRNA水平独立决定总生存期，一致性（c）指数分析表明，包含肿瘤分期、患者吸烟状态和循环Ang-2 mRNA水平信息的列线图定义具有更高的预测NSCLC患者总生存期的能力（c指数0.798）。这些结果表明，该列线图可作为确定NSCLC预后的独特实用工具，而不依赖于是否有足够的NSCLC手术或活检标本。根据我们的结果，循环Ang-2 mRNA水平也应纳入涉及靶向Ang-2的抗血管生成药物的临床前研究和临床试验设计中，以指导适当的患者分层和剂量选择，并将获益可能性提高到患者和临床医生可接受的水平。
