Tumoral and stromal expression of MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2, and VEGF-A in cervical cancer patient survival: a competing risk analysis

Autor(es)

Azevedo Martins, Jordana Maria ^[1] ; Rabelo-Santos, Silvia Helena ^[2] ; do Amaral Westin, Maria Cristina ^[3] ; Zeferino, Luiz Carlos ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Sch Med Sci, Dept Gynecol & Obstet, Tessalia Vieira de Camargo St 126, BR-13083887 Campinas, SP - Brazil

^[2] Univ Fed Goias, Sch Pharm, 240 St, BR-74605170 Goiania, Go - Brazil

^[3] Univ Estadual Campinas, UNICAMP, Lab Cytopathol, Womens Hlth Hosp Prof Jose Aristodemo Pinotti CAI, BR-13083881 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BMC CANCER; v. 20, n. 1 JUL 15 2020.
• Citações Web of Science: 0

Resumo

Background Expression of matrix metalloproteases 2, 9 and 14 (MMP-2, MMP-9, MMP-14), tissue inhibitors of metalloprotease 1 and 2 (TIMP-1, TIMP-2) and vascular endothelial growth factor A (VEGF-A) is involved in tumor invasion and metastasis via extracellular matrix degradation and angiogenesis. This study aimed to assess whether the expression of MMP-2, MMP-9, MMP-14, TIMP-1, and TIMP-2 in tumors and in the adjacent stroma is associated with cervical cancer prognosis. Methods This study analyzed a retrospective cohort of 64 patients. Protein expression was previously obtained by immunohistochemistry from biopsies containing both tumor and stroma. The expression and percentage of stained cells were categorized as high or low according to the cutoff points by using ROC curves. The follow-up data was collected from diagnosis to the last clinical visit. Clinical status categorized as alive without disease, alive with disease, death due to other causes, and death from the disease. The relative risk of death from the disease was evaluated according to the proteins expression using a cause-specific Cox regression model with a 95% confidence interval (95%CI). For the significant associations (p < 0.05), survival curves of patients with low and high expression were plotted for the competing risk survival curve analyses. Results High expression levels of stromal MMP-2 (RR; 95%CI: 3.91; 1.17-13.02) and stromal TIMP-2 (RR, 95%CI: 8.67; 1.15-65.27) were associated with a greater relative risk of death from the disease and with lower survival (p = 0.03;p = 0.04) than lower expression levels. Low expression levels of stromal MMP-9 (RR, 95%CI: 0.19; 0.05-0.65) and tumoral MMP-9 (HR, 95%CI: 0.19; 0.04-0.90) were protective factors against death from the disease and were associated with poorer survival. Conclusions High expression levels of MMP-2 and TIMP-2 in the stroma were significantly associated with poor survival in cervical cancer patients. High expression of MMP-9 was associated with a favorable cervical cancer prognosis. (AU)

• Processo FAPESP: 07/54709-0 - Papel das metaloproteinases da matriz extracelular (mmp-2, mmp-9 e mt-mmp) no processo de invasao tumoral da neoplasia do colo uterino
• Beneficiário: Luiz Carlos Zeferino
• Modalidade de apoio: Auxílio à Pesquisa - Regular