Pretreatment serum levels of matrix metalloproteinase-9 and vascular endothelial growth factor in non-small-cell lung cancer.
BACKGROUND
Matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF) are two proteins involved in angiogenesis. In the present study we investigated the association of pretreatment MMP-9 and VEGF serum levels with clinicopathological parameters and outcome in patients with non-small-cell lung cancer (NSCLC).


METHODS
From February 1998 to October 1999, pretreatment serum levels of MMP-9 and VEGF were analysed in 118 patients with enzyme-linked immunoassays. At diagnosis 50 patients (42%) were staged as early disease (I/II), 27 patients (23%) as locally advanced (IIIA/IIIB), and 41 patients (35%) had metastatic disease (IV). In 72 of the 118 patients tumours were resected and 46 patients received combination chemotherapy with gemcitabine and vinorelbine.


RESULTS
The median survival of all 118 patients was 602 days. The 72 patients who had undergone surgery had a median survival of 972 days and the 46 patients who were treated with chemotherapy had a median survival of 298 days (P <0.001). Resected patients with stage I/II disease and an MMP-9 serum level <or=1293 ng/ml or a VEGF serum level <or=630 pg/ml had a significantly longer survival (median survival longer than 1218 days) than patients with higher serum levels (median survival 421 days) (P = 0.001 for MMP-9; P = 0.04 for VEGF). No significant difference in survival was observed in patients with resected stage III disease. Besides tumour stage, Karnofsky performance status and gender, the pretreatment serum level of MMP-9 was identified as an independent prognostic factor in a multivariate Cox regression analysis.


CONCLUSIONS
Future studies may support our hypothesis that the pretreatment serum level of MMP-9 is a new powerful prognostic marker and can help to stratify NSCLC patients with stage I/II disease into low- and high-risk groups.
Laack
E
E
Department of Oncology and Haematology, University Hospital Hamburg-Eppendorf, Germany. laack@uke.uni-hamburg.de
Köhler
A
A
Kugler
C
C
Dierlamm
T
T
Knuffmann
C
C
Vohwinkel
G
G
Niestroy
A
A
Dahlmann
N
N
Peters
A
A
Berger
J
J
Fiedler
W
W
Hossfeld
D K
DK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016228:Endothelial Growth Factors / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006304:Health Status; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D008222:Lymphokines / Q000097:blood*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D013534:Survival; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine; D000093542:Gemcitabine
D014408:Biomarkers, Tumor; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003841:Deoxycytidine; D014747:Vinblastine; D020780:Matrix Metalloproteinase 9; D000077235:Vinorelbine; D000093542:Gemcitabine