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
Abstract 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 angiogen...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-07-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12885-020-07150-3 |
| _version_ | 1818325658738098176 |
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| author | Jordana Maria Azevedo Martins Silvia Helena Rabelo-Santos Maria Cristina do Amaral Westin Luiz Carlos Zeferino |
| author_facet | Jordana Maria Azevedo Martins Silvia Helena Rabelo-Santos Maria Cristina do Amaral Westin Luiz Carlos Zeferino |
| author_sort | Jordana Maria Azevedo Martins |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-13T11:47:59Z |
| format | Article |
| id | doaj.art-f0a70c89dbb847f998f2da8ea3647b40 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-13T11:47:59Z |
| publishDate | 2020-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-f0a70c89dbb847f998f2da8ea3647b402022-12-21T23:47:28ZengBMCBMC Cancer1471-24072020-07-0120111110.1186/s12885-020-07150-3Tumoral 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 analysisJordana Maria Azevedo Martins0Silvia Helena Rabelo-Santos1Maria Cristina do Amaral Westin2Luiz Carlos Zeferino3Department of Gynecology and Obstetrics, School of Medical Sciences, State University of Campinas, UNICAMPSchool of Pharmacy, Federal University of GoiasLaboratory of Cytopathology, Women’s Health Hospital Professor Jose Aristodemo Pinotti – (CAISM), University of Campinas (UNICAMP)Department of Gynecology and Obstetrics, School of Medical Sciences, State University of Campinas, UNICAMPAbstract 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.http://link.springer.com/article/10.1186/s12885-020-07150-3Uterine cervical neoplasmsMatrix metalloproteinase 2Matrix metalloproteinase 9Tissue inhibitor of Metalloproteinase-2Tumor microenvironmentStroma |
| spellingShingle | Jordana Maria Azevedo Martins Silvia Helena Rabelo-Santos Maria Cristina do Amaral Westin Luiz Carlos Zeferino 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 BMC Cancer Uterine cervical neoplasms Matrix metalloproteinase 2 Matrix metalloproteinase 9 Tissue inhibitor of Metalloproteinase-2 Tumor microenvironment Stroma |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Uterine cervical neoplasms Matrix metalloproteinase 2 Matrix metalloproteinase 9 Tissue inhibitor of Metalloproteinase-2 Tumor microenvironment Stroma |
| url | http://link.springer.com/article/10.1186/s12885-020-07150-3 |
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