Expression spectra of matrix metalloproteinases in metastatic non-small cell lung cancer.
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.
Lin
Torng-Sen
TS
Department of Surgery, Chang-Hua Christian Hospital, and Institute of Medicine, Chang-Shan Medical University, Taichung, Taiwan.
Chiou
Shiow-Her
SH
Wang
Liang-Shun
LS
Huang
Hsuan-Hua
HH
Chiang
Shu-Fen
SF
Shih
Alex Y H
AY
Chen
Ya-Lin
YL
Chen
Chih-Yi
CY
Hsu
Chung-Ping
CP
Hsu
Nan-Yung
NY
Chou
Ming-Chih
MC
Kuo
Shou-Jen
SJ
Chow
Kuan-Chih
KC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary*; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D009693:Nucleic Acid Hybridization; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013382:Subtraction Technique; D015996:Survival Rate
D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D012334:RNA, Neoplasm; D020782:Matrix Metalloproteinases