Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210002, China.
Med Oncol. 2012 Dec;29(4):2633-9. doi: 10.1007/s12032-012-0180-5. Epub 2012 Feb 22.
ADAM28 (a disintegrin and metalloproteinase 28) is over-expressed in non-small cell lung cancer (NSCLC) with correlation to cancer proliferation, tumor size and lymph node metastasis. In the present study, we investigated the predictive and prognostic value of ADAM28 during chemotherapy in patients with advanced NSCLC. 122 advanced NSCLC cases, 37 patients with benign lung disease and 40 healthy controls were enrolled in the study. The serum levels of ADAM28 were measured by enzymelinked immunosorbent assays. Data were correlated with diagnosis, radiologic objective response and survival. Serum levels of ADAM28 in advanced NSCLC group were significantly elevated compared to benign lung disease group (P<0.001) and healthy controls (P<0.001). And the expression of ADAM28 had relationship to the tumor size and lymph metastasis in NSCLC patients. When the cut-off value of ADAM28 was 225.54 pg/ml, the area under the ROC curve was 0.843 (95% confidence interval [CI]: 0.784-0.902); the sensitivity (SEN) and specificity (SPE) were both the best, with a SEN of 76% and a SPE of 83%. The patients who had ADAM28-response and no ADAM28-response had significantly difference in objective response to treatment (P<0.001). The median Progression-free survival from response assessment was 5 months. In the multivariate analysis, performance status (hazard ratio [HR], 1.68; 95% CI: 1.06-2.67), the level of serum ADAM28 (HR, 1.01; 95% CI: 1.01-1.02), and ADAM28-responses (HR, 047; 95% CI, 0.26-0.83), were significant correlated with prognosis. The levels of ADAM28 and ADAM28-responses appeared to be reliable surrogate markers to predict tumor response and survival in patients with advanced NSCLC.
ADAM28（解整合素和金属蛋白酶 28）在非小细胞肺癌（NSCLC）中过度表达，与癌症增殖、肿瘤大小和淋巴结转移有关。本研究旨在探讨 ADAM28 在晚期 NSCLC 患者化疗中的预测和预后价值。纳入 122 例晚期 NSCLC 患者、37 例良性肺部疾病患者和 40 例健康对照者。采用酶联免疫吸附试验检测 ADAM28 血清水平。数据与诊断、影像学客观反应和生存相关。与良性肺部疾病组（P<0.001）和健康对照组（P<0.001）相比，晚期 NSCLC 组的 ADAM28 血清水平显著升高。ADAM28 的表达与 NSCLC 患者的肿瘤大小和淋巴结转移有关。当 ADAM28 的截断值为 225.54pg/ml 时，ROC 曲线下面积为 0.843（95%置信区间[CI]：0.784-0.902）；灵敏度（SEN）和特异性（SPE）均最佳，SEN 为 76%，SPE 为 83%。有 ADAM28 反应和无 ADAM28 反应的患者在治疗客观反应方面有显著差异（P<0.001）。从反应评估开始的中位无进展生存期为 5 个月。在多因素分析中，表现状态（风险比[HR]，1.68；95%CI：1.06-2.67）、血清 ADAM28 水平（HR，1.01；95%CI：1.01-1.02）和 ADAM28 反应（HR，0.47；95%CI，0.26-0.83）与预后相关。ADAM28 水平和 ADAM28 反应似乎是预测晚期 NSCLC 患者肿瘤反应和生存的可靠替代标志物。
