Maruno K, Yamaguchi K, Abe K, Suzuki M, Saijo N, Mishima Y, Yanaihara N, Shimosato Y
Growth Factor Division, National Cancer Center Research Institute, Japan.
Cancer Res. 1989 Feb 1;49(3):629-32.
Gastrin-releasing peptide (GRP) is now known to be a very common product of small cell lung carcinoma (SCLC). With the aim of investigating the possible role of this peptide as a tumor marker of SCLC, we have developed a sensitive radioimmunoassay system for plasma immunoreactive GRP using immune-affinity chromatography for plasma extraction. Plasma immunoreactive GRP levels in control subjects were determined by using 15 ml of plasma as the starting material (minimum concentration detectable, 0.8 pg/ml). The levels in 10 control subjects were (mean +/- SD) 1.2 +/- 0.27 pg/ml; range, 0.86-1.7 pg/ml. This assay system was applied for the clinical use by using 3 ml of plasma as the starting material (minimum concentration detectable, 4.0 pg/ml). Plasma immunoreactive GRP levels were elevated in SCLC patients at frequencies of 71% in patients with limited disease and 80% in those with extensive disease. Furthermore, a change in the level showed excellent correlation with the therapeutic response. In six patients with complete response who had had elevated levels before treatment, the levels decreased to an undetectable range when the tumor disappeared, and they remained undetectable until 1 month later, when the patients were judged to have achieved complete response. In the partial response group, plasma immunoreactive GRP levels had decreased to an undetectable level in two of three patients, when the patients achieved partial response. In four patients with progressive disease, plasma immunoreactive GRP levels were elevated at the time of the progressive disease judgment, when compared with levels before treatment. The levels in 21 patients with non-SCLC (10 with adenocarcinoma, seven with squamous cell carcinoma and four with large cell carcinoma) were not elevated. These results indicate the plasma immunoreactive GRP level as a useful tumor marker in SCLC patients. It is now believed that GRP can function as an autocrine growth factor for SCLC. The present study suggests that the possible autocrine growth factor could serve as a reliable tumor marker for cancer patients.
胃泌素释放肽（GRP）现已被认为是小细胞肺癌（SCLC）非常常见的产物。为了研究这种肽作为SCLC肿瘤标志物的可能作用，我们开发了一种灵敏的放射免疫分析系统，用于检测血浆中免疫反应性GRP，该系统采用免疫亲和层析法提取血浆。以15 ml血浆作为起始材料（可检测的最低浓度为0.8 pg/ml），测定了对照受试者血浆中免疫反应性GRP水平。10名对照受试者的水平为（平均值±标准差）1.2±0.27 pg/ml；范围为0.86 - 1.7 pg/ml。该分析系统以3 ml血浆作为起始材料（可检测的最低浓度为4.0 pg/ml）用于临床应用。SCLC患者血浆免疫反应性GRP水平升高，局限期患者的升高频率为71%，广泛期患者为80%。此外，该水平的变化与治疗反应具有良好的相关性。在6例治疗前水平升高的完全缓解患者中，肿瘤消失时水平降至不可检测范围，直至1个月后患者被判定达到完全缓解时仍不可检测。在部分缓解组中，3例患者中有两例在达到部分缓解时血浆免疫反应性GRP水平降至不可检测水平。在4例疾病进展患者中，与治疗前水平相比，在疾病进展判定时血浆免疫反应性GRP水平升高。21例非SCLC患者（10例腺癌、7例鳞状细胞癌和4例大细胞癌）的水平未升高。这些结果表明血浆免疫反应性GRP水平是SCLC患者有用的肿瘤标志物。现在认为GRP可作为SCLC的自分泌生长因子。本研究表明，这种可能的自分泌生长因子可作为癌症患者可靠的肿瘤标志物。
