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R Gallego, Oncology, Hospital Clinico Barcelona, Barcelona, 08036, Spain
J Codony-Servat, Biology, Hospital Clinic Barcelona, Barcelona, Spain
X Garcia-Albeniz, Oncology, Hospital Clinic Barcelona, Barcelona, Spain
E Carcereny, Oncology, Hospital Clinic Barcelona, Barcelona, Spain
R Longaron, Biology, Hospital Clinic Barcelona, Barcelona, Spain
A Olivera, Oncology, Hospital Clinic Barcelona, Barcelona, Spain
M Tosca, Oncology, Hospital Clinic Barcelona, Barcelona, Spain
J Auge, Biochemical, Hospital Clinic Barcelona, Barcelona, Spain
P Gascon, Oncology, Hospital Clinic Barcelona, Barcelona, Spain
J Maurel, Oncology, Hospital Clinic Barcelona, Barcelona, Spain

Correspondence: Rosa Gallego, Email: rgallego{at}clinic.ub.es

Abstract

ABSTRACT

Insulin-like growth factor-I (IGF-I) is thought to have antiapoptotic and mitogenic properties in colorectal cancer, whereas IGF binding protein-3 (IGFBP-3) seems to exert a pro-apoptotic effect. Additionally, matrix metalloproteinase-7 (MMP-7), an enzyme with in vitro ability to degrade IGFBP-3, has been shown to be a prognostic factor in advanced colorectal cancer (ACRC). We studied whether chemotherapy treatment for ACRC modulates IGF-I, IGFBP-3 and MMP-7 serum levels.

In 41 patients undergoing first-line therapy for ACRC, serum levels of IGF-I, IGFBP-3 and MMP-7 were measured with immunoassays at baseline and every 3 months until progressive disease, or a maximum of 5 determinations, during a chemotherapy regimen of either FOLFOX or FOLFIRI therapies. An average of 4 extractions (range 3 to 5) were done, for a total of 157 determinations. Mean pre-treatment values of IGF-I, IGFBP-3 and MMP-7 were 83 (95% CI, 73-92) ng/ml, 2372 (95% CI, 2121-2623) ng/ml and 10.6 (95% CI, 7.21-13.98) ng/ml, respectively. No significant changes in IGF-I were found, but a significant increase in IGFBP-3 serum concentrations was observed during or after chemotherapy treatment without progressive disease, compared with basal levels (p<0.001). A significant decrease of IGFBP-3 to 1983 ng/ml (95% CI, 1675-2292) and a significant increase of MMP-7 levels to 14.6 (7.6-21.7) ng/ml were observed at progression of disease compared to baseline and treatment levels (p<0.001).

This study shows that IGFBP-3 and MMP-7 serum levels change during chemotherapy treatment. The increased MMP-7 levels at disease progression supports the hypothesis that this protease could play a role in acquired resistance by degrading IGFBP-3.

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