Matrix metalloproteinase 7 is a useful marker for 5-fluorouracil-based adjuvant chemotherapy in stage II and stage III colorectal cancer patients.
Matrix metalloproteinase 7 (MMP7) was reported to be a negative regulator in Fas-mediated apoptosis. The mechanism of cell killing associated with 5-FU treatment in colon cancer was also closely related to Fas-induced apoptosis, which implied that the expression level of MMP7 in colorectal cancer may be associated with the sensitivity of 5-FU treatment. To prove the hypothesis, first we verified the negative relevance between the colorectal cancer cells apoptosis in response to 5-FU treatment and MMP7 level by MTT and flow cytometry assay in vitro. Further, we found the apoptosis was in a positive relation with the Fas ligand level collected from the medium, suggesting a Fas-induced apoptosis. We found that increased level of MMP7 resulted in the enhanced drug resistance in SW620 colon cancer cells treated with 5-FU in vitro. Besides, we analyzed the influence of MMP7 on prognosis of 76 patients with TNM stage II-III colorectal cancers who had undergone curative resections and received 5-FU-based adjuvant chemotherapy. The expression of MMP7 was detected by IHC, and the relationship between the expression of MMP7 and disease-free survival was analyzed by univariate analysis and multivariate analysis. Patients with higher expression of MMP7 showed inferior disease-free survival (p=0.007), and high expression of MMP7 was a significant independent unfavorable prognostic factor (p=0.012). These data suggested that MMP7 is a useful marker for 5-FU chemotherapy sensitivity in patients with stage II-III colorectal cancer.
Department of Radio-Chemo Therapy, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China.
Yong
Y
Huang
Haijun
H
Yu
Han
H
Lei
Conghua
C
Xie
Yahua
Y
Zhong
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005472:Fluorouracil / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; D005472:Fluorouracil