Elevated serum levels of type I collagen degradation marker ICTP and tissue inhibitor of metalloproteinase (TIMP) 1 are associated with poor prognosis in lung cancer.
OBJECTIVE
The aim of this study was to evaluate the correlation between type I collagen degradation marker ICTP, MMP (matrix metalloproteinase)-9, and tissue inhibitor of metalloproteinase (TIMP)-1 and to compare their value as prognostic factors in lung cancer.


METHODS
From the sera of 141 lung cancer patients, we assessed markers of type I collagen synthesis (PINP and PICP) and degradation (ICTP) by radioimmunoassays, and we assessed MMP-9 and its tissue inhibitor TIMP-1 by ELISA. There were 62 squamous cell carcinomas, 42 adenocarcinomas, 14 small cell carcinomas, and 23 cases with other histology. Seventeen of these patients had advanced disease. Sixty-seven patients had been operated on, 33 had received radiation therapy, 7 had received chemotherapy, and the rest had received other treatment combinations.


RESULTS
We examined the relationship between these markers and found a correlation between ICTP and MMP-9 (r = 0.201; P = 0.01) or TIMP-1 (r = 0.415; P = 0.00). Elevated serum concentrations of ICTP (>5 microg/liter) and/or TIMP-1 (>300 ng/ml) correlated with poor prognosis. In univariate regression analysis, ICTP had prognostic value (odds ratio, 1.6462; P < 0.03): the patients with elevated serum concentrations of ICTP (>5 microg/liter) had a 64% higher risk of dying from lung cancer than did patients with opposite values.


CONCLUSIONS
Our results indicated that ICTP and TIMP-1 are good prognostic markers in lung cancer. The association between serum MMP-9 and ICTP suggests that MMP-9 could play a role in the degradation of the extracellular matrix producing ICTP in this pathological situation.
Ylisirniö
S
S
Departments of Oncology and Radiotherapy, Oulu University Hospital, FIN-90220 Oulu, Finland.
Höyhtyä
M
M
Mäkitaro
R
R
Pääakkö
P
P
Risteli
J
J
Kinnula
V L
VL
Turpeenniemi-Hujanen
T
T
Jukkola
A
A
D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D018288:Carcinoma, Small Cell / Q000097:blood / Q000175:diagnosis; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000175:diagnosis; D003094:Collagen / Q000097:blood*; D024042:Collagen Type I; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis*; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000097:blood; D008875:Middle Aged; D010455:Peptides / Q000097:blood*; D011379:Prognosis; D011863:Radioimmunoassay; D012044:Regression Analysis; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
D014408:Biomarkers, Tumor; D024042:Collagen Type I; D010455:Peptides; D019715:Tissue Inhibitor of Metalloproteinase-1; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; D020784:Matrix Metalloproteinase 8