Lin Torng-Sen, Chiou Shiow-Her, Wang Liang-Shun, Huang Hsuan-Hua, Chiang Shu-Fen, Shih Alex Y H, Chen Ya-Lin, Chen Chih-Yi, Hsu Chung-Ping, Hsu Nan-Yung, Chou Ming-Chih, Kuo Shou-Jen, Chow Kuan-Chih
Department of Surgery, Chang-Hua Christian Hospital, and Institute of Medicine, Chang-Shan Medical University, Taichung, Taiwan.
Oncol Rep. 2004 Oct;12(4):717-23.
By combining suppression subtractive hybridization and microarray to examine gene expressions between metastatic and non-metastatic non-small cell lung cancer (NSCLC), we have identified differential expression spectra of matrix metalloproteinases (MMP). Among MMPs, expressions of MMP-13, -14, -15 and -24 decreased, those of MMP-9, -11, -12, -16, -17, -19 and -23B did not change, and those of MMP-1, -2, -7, -8 and -10 increased dramatically. Overexpressions of MMP-1, -2, -7 and -10 were confirmed by reverse transcription-polymerase chain reaction. In this study we further assessed the clinical significance of MMP-1, -2, -7 and -10. Specimens from 472 patients with completely resected NSCLC were examined by immunohistochemistry. The median follow-up period was 38 months (range, 2-113 months). Overexpression of MMP-1 was observed in 72.9% (n=344) of 472 patients, that of MMP-2 was 77.9% (n=352), MMP-7 63.3% (n=299) and that of MMP-10 was 27.1% (n=128). For patients with lymph node metastasis, MMP-1 and -2 overexpressions were not only independent prognostic factors for unfavorable outcome, but also associated with decreased survival (p=0.0015, and p=0.011 respectively). The present study showed that MMP expression spectrum in NSCLC was heterogeneous: expression of some MMP increased, some unchanged, while some decreased. Therefore, it should be worth determining MMP expression pattern as a regimen reference for NSCLC patients who were scheduled to receive MMP inhibitor, which was class-specific, as adjuvant therapeutic agent.
通过结合抑制性消减杂交和微阵列技术来检测转移性和非转移性非小细胞肺癌（NSCLC）之间的基因表达，我们已经鉴定出基质金属蛋白酶（MMP）的差异表达谱。在MMP中，MMP-13、-14、-15和-24的表达下降，MMP-9、-11、-12、-16、-17、-19和-23B的表达未改变，而MMP-1、-2、-7、-8和-10的表达显著增加。通过逆转录-聚合酶链反应证实了MMP-1、-2、-7和-10的过表达。在本研究中，我们进一步评估了MMP-1、-2、-7和-10的临床意义。对472例完全切除的NSCLC患者的标本进行免疫组织化学检查。中位随访期为38个月（范围2-113个月）。472例患者中，72.9%（n=344）的患者MMP-1过表达，77.9%（n=352）的患者MMP-2过表达，63.3%（n=299）的患者MMP-7过表达，27.1%（n=128）的患者MMP-10过表达。对于有淋巴结转移的患者，MMP-1和-2的过表达不仅是不良预后的独立预测因素，而且与生存率降低相关（分别为p=0.0015和p=0.011）。本研究表明，NSCLC中MMP表达谱是异质性的：一些MMP的表达增加，一些不变，而一些下降。因此，对于计划接受具有类别特异性的MMP抑制剂作为辅助治疗剂的NSCLC患者，确定MMP表达模式作为治疗参考可能是值得的。
