Pretreatment serum levels of matrix metalloproteinase-9 and vascular endothelial growth factor in non-small-cell lung cancer

Laack, Eckart; Köhler, Annika; Kugler, C.; Dierlamm, T.; Knuffmann, C.; Vohwinkel, Gabi; Niestroy, A.; Dahlmann, N; Peters, A. M.; Berger, Jürgen; Fiedler, Walter; Hossfeld, D. K.

doi:10.1093/annonc/mdf270

Cited by 86 publications

(72 citation statements)

References 29 publications

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“…In agreement with previous studies (Laack et al, 2002;Chakra et al, 2008). we found that a high serum VEGF level did not independently determine prognosis of lung cancer.But several other studies produced conflicting results (Kaya et al, 2004;Hasegawa et al, 2005).…”

Section: Discussionsupporting

confidence: 93%

Prognostic Values of VEGF and Endostatin with Malignant Pleural Effusions in Patients with Lung Cancer

Yu¹,

Lu²,

Xia³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Aims: Angiogenesis is important in malignant pleural effusion (MPE) formation and it is regulated by a number of pro-and anti-angiogenic cytokines. The purpose of this study was to evaluate the prognostic value of angiogenic factor vascular endothelial growth factor (VEGF) and angiogenesis inhibitor endostatin in lung cancer patients with MPE, and investigate the relationship between these two kinds of agent. Methods: Using enzyme-linked immunoadsorbent assay, the concentrations of VEGF and endostatin were measured in pleural effusions (PE) and serum from a total of 70 lung cancer patients with MPE and 20 patients with tuberculosis. Results: Compared to patients with tuberculosis, the levels of VEGF and endostatin in both PE and serum were significantly higher in patients with lung cancer. There were statistically significant correlations between VEGF levels in PE and serum (r=0.696, p<0.001), endostatin levels in PE and serum (r=0.310, p=0.022), and VEGF and endostatin levels in PE (r=0.287, p=0.019). Cox multivariate analysis revealed that elevated pleural VEGF and endostatin levels and serum endostatin level were independent predictors of shorter overall survival. Conclusion: Both pro-and anti-angiogenic factors are likely contributors to PE formation. Our results suggest that the levels of VEGF and endostatin in PE, together with endostatin in serum, may be potential prognostic parameters for lung cancer patients with MPE.

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Section: Discussionsupporting

confidence: 93%

Prognostic Values of VEGF and Endostatin with Malignant Pleural Effusions in Patients with Lung Cancer

Yu¹,

Lu²,

Xia³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…22 There are, however, few previous publications report that serum MMP-9 would have any prognostic role in cancer patients. [15][16][17][18] The prognosis of squamous cell carcinoma of head and neck is traditionally linked to the TNM stage, differentiation (grade) and performance status. However, these factors are not sufficient enough to predict outcome accurately.…”

Section: Discussionmentioning

confidence: 99%

“…[11][12][13][14] Recently, increased serum MMP-9 and MMP-2 levels have been reported to be practical in predicting disease prognosis in some types of tumors. [15][16][17][18] Several studies have shown that gelatinases are expressed in head and neck carcinoma cells, and gelatinases may take part in the progression and invasion of these tumors. [19][20][21] We have recently found that MMP-9 positivity in immunohistochemical staining is associated with unfavorable prognosis in head and neck squamous cell carcinoma.…”

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confidence: 99%

Serum matrix metalloproteinase‐9 in head and neck squamous cell carcinomais a prognostic marker

Ruokolainen

Pääkkö

Turpeenniemi‐Hujanen

2005

Intl Journal of Cancer

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The aim of this study was to determine whether serum matrix metalloproteinase-9 (MMP-9) could predict cause-specific and relapse-free survival in patients with squamous cell carcinoma of head and neck. Furthermore, this study was designed to investigate whether there is an association between MMP-9 immunohistochemical staining and serum MMP-9 levels. Pretreatment serum levels of MMP-9 were quantitatively measured by ELISA assay in 67 patients presenting with a primary head and neck squamous cell carcinoma. The results were compared with the corresponding immunohistochemical staining results, clinical data and the patients' outcome. The follow-up time for all of the patients was at least 5 years. There was a statistically significant correlation between circulating MMP-9 and MMP-9 immunohistochemical staining in the corresponding tumors (p 5 0.028). The cause-specific and relapse-free survival rates were clearly lower among patients with high MMP-9 serum levels (> 73 ng/ml). The 5-year cause-specific survival-rate was 40% in a patient group with high serum MMP-9, and 69% for patients with a low MMP-9 level (p 5 0.027). In the same follow-up period, the cumulative relapsefree survival rate was 36% in patients presenting with a high serum MMP-9 and 66% in those with a low MMP-9 level. No correlation was found between MMP-9 serum levels and the traditional clinical or histopathologic factors. The results suggest for the first time that pretreatment serum MMP-9 level could serve as a prognostic factor in head and neck squamous cell carcinoma. ' 2005 Wiley-Liss, Inc.

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“…In comparison with healthy controls, the serum levels of MMP-9 are elevated in head and neck squamous cell carcinoma (23,24) and in colon (25), gastric (26), bladder, breast, and prostate cancer (27). Furthermore, elevated MMP-9 serum levels have been shown to correlate with poor survival in stage I to II non -small cell lung cancer patients (28).…”

mentioning

confidence: 99%

High Serum Levels of Matrix Metalloproteinase-9 and Matrix Metalloproteinase-1 Are Associated with Rapid Progression in Patients with Metastatic Melanoma

Nikkola

Vihinen

Vuoristo

et al. 2005

Clinical Cancer Research

166

127

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Purpose: Matrix metalloproteinases (MMP) are proteolytic enzymes that play an important role in various aspects of cancer progression. In the present work, we have studied the prognostic significance of serum levels of gelatinase B (MMP-9), collagenase-1 (MMP-1), and collagenase-3 (MMP-13) in patients with advanced melanoma. Experimental Design: Total pretreatment serum levels of MMP-9 in 71patients and MMP-1and MMP-13 in 48 patients were determined by an assay system based on ELISA. Total MMP levels were also assessed in eight healthy controls. The active and latent forms of MMPs were defined by usingWestern blot analysis and gelatin zymography. Results: Patients with high serum levels of MMP-9 (z376.6 ng/mL; n = 19) had significantly poorer overall survival (OS) than patients with lower serum MMP-9 levels (n = 52; median OS, 29.1 versus 45.2 months; P = 0.033). High MMP-9 levels were also associated with visceral or bone metastasis (P = 0.027), elevated serum alkaline phosphatase level (P = 0.0009), and presence of liver metastases (P = 0.032). Serum levels of MMP-1and MMP-13 did not correlate with OS. MMP-1 and MMP-9 were found mainly in latent forms in serum, whereas the majority of MMP-13 in serum was active (48 kDa) form. MMP-13 was found more often in active form in patients (mean, 99% of the total MMP-13 level) than in controls (mean, 84% of the total MMP-13 level; P < 0.0001). After initiating the therapy, patients with elevated levels of MMP-1 (z29.8 ng/mL, n = 10) progressed more rapidly than patients with lower levels (median, 1.9 versus 3.5 months; P = 0.023). Serum levels of MMP-9 and MMP-13 did not correlate with the time to progression (TTP). In multivariate analysis with age and gender, MMP-9 or MMP-1turned out to be independent prognostic factors for OS [P = 0.039; hazard ratio (HR), 1.8; 95% confidence interval (95% CI), 1.03-3.3] or TTP (P = 0.023; HR, 2.7; 95% CI, 1.15-6.4), respectively. Conclusions: Our findings provide evidence that MMP-1, MMP-9, and MMP-13 play important roles at different phases of metastatic melanoma spread and that serum MMP-9, in particular, could have clinical value in identifying patients at high risk for melanoma progression.

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Pretreatment serum levels of matrix metalloproteinase-9 and vascular endothelial growth factor in non-small-cell lung cancer

Abstract: Future studies may support our hypothesis that the pretreatment serum level of MMP-9 is a new powerful prognostic marker and can help to stratify NSCLC patients with stage I/II disease into low- and high-risk groups.

Cited by 86 publications

References 29 publications

Prognostic Values of VEGF and Endostatin with Malignant Pleural Effusions in Patients with Lung Cancer

Prognostic Values of VEGF and Endostatin with Malignant Pleural Effusions in Patients with Lung Cancer

Serum matrix metalloproteinase‐9 in head and neck squamous cell carcinomais a prognostic marker

High Serum Levels of Matrix Metalloproteinase-9 and Matrix Metalloproteinase-1 Are Associated with Rapid Progression in Patients with Metastatic Melanoma

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