Nisman Benjamin, Heching Norman, Biran Haim, Barak Vivian, Peretz Tamar
Department of Oncology, Hadassah University Hospital, Jerusalem, Israel.
Tumour Biol. 2006;27(1):8-16. doi: 10.1159/000090151. Epub 2005 Dec 8.
Chromogranin A (CGA), Pro-gastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) are known as immunohistochemical tissue markers closely associated with neuroendocrine differentiation in non-small-cell lung carcinoma (NSCLC). The aim of the present study was to assess the value of serum levels of these markers in predicting response to chemotherapy and survival of patients with unresectable NSCLC.
The study included 67 patients with advanced NSCLC treated with chemotherapy. Before treatment, serum levels of CGA, ProGRP and NSE were measured with commercial kits.
No association was found between serum NSE and age, gender, histology, performance status or extent of the disease. Distribution of serum CGA differed significantly according to gender and histology, with higher levels being found in men (p = 0.01) and in squamous cell carcinoma (p = 0.01). Serum ProGRP levels correlated with disease extent, being higher in patients with metastatic disease (M1) than in those with locoregional disease (M0; p = 0.02). The association of NSE, CGA and ProGRP levels with response to chemotherapy was not significant. While NSE had no impact on survival, the median survival was shorter for patients with elevated serum CGA and longer for patients with high ProGRP levels. Association with survival was significant when the Classification and Regression Tree (CART)-derived or median cutoff points were explored. On inclusion in multivariate Cox models, both CGA and ProGRP retained significance with high levels showing an opposite effect on survival [CART-derived cutoff points: CGA, relative risk (RR) -4.0; p < 0.001, and ProGRP, RR -0.4; p = 0.006, and median cutoff points: CGA, RR -1.8; p = 0.04, and ProGRP, RR -0.5; p = 0.03]. The combined use of CGA, ProGRP and NSE allowed for definition of two sets of patients with significantly different median survival times (25.2 vs. 8.8 months, p = 0.0001).
In the circulation, CGA and Pro-GRP appear to bear important information related to the prognosis for NSCLC patients before chemotherapy. While a high CGA before treatment was found as an unfavorable prognostic determinant, a high ProGRP conferred a survival advantage. The combined use of serum CGA, ProGRP and NSE may supply additional information to prognosis.
嗜铬粒蛋白A（CGA）、胃泌素释放肽前体（ProGRP）和神经元特异性烯醇化酶（NSE）是已知的与非小细胞肺癌（NSCLC）神经内分泌分化密切相关的免疫组织化学组织标志物。本研究的目的是评估这些标志物的血清水平在预测不可切除NSCLC患者化疗反应和生存情况中的价值。
本研究纳入了67例接受化疗的晚期NSCLC患者。治疗前，使用商用试剂盒检测血清CGA、ProGRP和NSE水平。
血清NSE与年龄、性别、组织学类型、体能状态或疾病范围之间未发现关联。血清CGA水平的分布根据性别和组织学类型有显著差异，男性（p = 0.01）和鳞状细胞癌患者（p = 0.01）的水平较高。血清ProGRP水平与疾病范围相关，转移性疾病（M1）患者的水平高于局限性疾病（M0）患者（p = 0.02）。NSE、CGA和ProGRP水平与化疗反应的关联不显著。虽然NSE对生存无影响，但血清CGA升高的患者中位生存期较短，而ProGRP水平高的患者中位生存期较长。当探索分类与回归树（CART）衍生的或中位数截断点时，与生存的关联具有显著性。纳入多变量Cox模型后，CGA和ProGRP均保持显著性，高水平对生存显示出相反的影响[CART衍生的截断点：CGA，相对风险（RR）-4.0；p < 0.001，ProGRP，RR -0.4；p = 0.006，中位数截断点：CGA，RR -1.8；p = 0.04，ProGRP，RR -0.5；p = 0.03]。联合使用CGA、ProGRP和NSE可定义两组中位生存时间显著不同的患者（25.2对8.8个月，p = 0.0001）。
在循环中，CGA和Pro-GRP似乎携带了与NSCLC患者化疗前预后相关的重要信息。虽然治疗前CGA水平高被发现是一个不利的预后决定因素，但ProGRP水平高则赋予生存优势。联合使用血清CGA、ProGRP和NSE可能为预后提供额外信息。
