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Matrix metalloproteinase-9 and -2 and tissue inhibitor of matrix metalloproteinase-2 in invasive pituitary adenomas

View Article: PubMed Central - PubMed

ABSTRACT

The extracellular matrix is important for tumor invasion and metastasis. Normal function of the extracellular matrix depends on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The objective of this meta-analysis was to assess the relationship between expression of MMP-9, MMP-2, and TIMP-2 and invasion of pituitary adenomas.

We searched Pubmed, Embase, and the Chinese Biomedical Database up to October 2015. RevMan 5.1 software (Cochrane Collaboration, Copenhagen, Denmark) was used for statistical analysis. We calculated the standardized mean difference (SMD) for data expressed as mean ± standard deviation because of the difference in the detection method.

Twenty-four studies (1320 patients) were included. MMP-9 expression was higher in the patients with invasive pituitary adenomas (IPAs) than patients with noninvasive pituitary adenomas (NIPAs) with detection methods of IHC [odds ratio (OR) = 5.48, 95% confidence interval (CI) = 2.61–11.50, P < 0.00001), and reverse transcriptase-polymerase chain reaction (SMD = 2.28, 95% CI = 0.91–3.64, P = 0.001). MMP-2 expression was also increased in patients with IPAs at the protein level (OR = 3.58, 95% CI = 1.63–7.87, P = 0.001), and RNA level (SMD = 3.91, 95% CI = 1.52–6.29, P = 0.001). Meta-analysis showed that there was no difference in TIMP-2 expression between invasive and NIPAs at the protein level (OR = 0.38, 95% CI = 0.06–2.26, P = 0.29). MMP-9 expression in prolactinomas and nonfunctioning pituitary adenomas was also no difference (OR = 1.03, 95% CI = 0.48–2.20, P = 0.95).

The results indicated that MMP-9 and -2 may be correlated with invasiveness of pituitary adenomas, although their relationship with functional status of pituitary adenomas is still not clear. TIMP-2 expression in IPAs needs to be investigated further.

No MeSH data available.


Related in: MedlinePlus

Forest plots for the relationship between MMP-2 expression and tumor invasiveness of PAs (A) at the protein level and (B) at the RNA level. M-H = Mantel–Haenszel test, IV = inverse variance, Random = a random effects model, CI = confidence intervals.
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Figure 3: Forest plots for the relationship between MMP-2 expression and tumor invasiveness of PAs (A) at the protein level and (B) at the RNA level. M-H = Mantel–Haenszel test, IV = inverse variance, Random = a random effects model, CI = confidence intervals.

Mentions: At the protein level or RNA level, there was substantial heterogeneity among the studies, making the use of a random effects model. Fourteen studies (374 IPAs and 328 NIPAs) and seven studies (146 IPAs and 126 NIPAs) showed MMP-9 expression at the protein level and RNA level, respectively. The results indicated that when we compared patients with invasive and NIPAs, MMP-9 expression was higher in the former with detection methods of IHC (OR = 5.48, 95% CI = 2.61–11.50, P < 0.00001; Fig. 2A), and RT-PCR (SMD = 2.28, 95% CI = 0.91–3.64, P = 0.001; Fig. 2B). Seven studies (207 IPAs and 184 NIPAs) and four studies (91 IPAs and 97 NIPAs) showed MMP-2 expression at the protein level and RNA level, respectively. MMP-2 expression was increased in patients with IPAs at the protein level (OR = 3.58, 95% CI = 1.63–7.87, P = 0.001; Fig. 3A), and RNA level (SMD = 3.91, 95% CI = 1.52–6.29, P = 0.001; Fig. 3B). The results of Sensitivity analysis indicated that no single study had a significant influence on the above four-pooled effect sizes (Supplemental Table S2–S5). Subgroup analytical results found that detection methods had no influence on pooled SMD of MMP-9 (test for subgroup differences: I2 = 0%, P = 0.64; Fig. 2B) and MMP-2 (I2 = 0%, P = 0.97; Fig. 3B) at the RNA level.


Matrix metalloproteinase-9 and -2 and tissue inhibitor of matrix metalloproteinase-2 in invasive pituitary adenomas
Forest plots for the relationship between MMP-2 expression and tumor invasiveness of PAs (A) at the protein level and (B) at the RNA level. M-H = Mantel–Haenszel test, IV = inverse variance, Random = a random effects model, CI = confidence intervals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998479&req=5

Figure 3: Forest plots for the relationship between MMP-2 expression and tumor invasiveness of PAs (A) at the protein level and (B) at the RNA level. M-H = Mantel–Haenszel test, IV = inverse variance, Random = a random effects model, CI = confidence intervals.
Mentions: At the protein level or RNA level, there was substantial heterogeneity among the studies, making the use of a random effects model. Fourteen studies (374 IPAs and 328 NIPAs) and seven studies (146 IPAs and 126 NIPAs) showed MMP-9 expression at the protein level and RNA level, respectively. The results indicated that when we compared patients with invasive and NIPAs, MMP-9 expression was higher in the former with detection methods of IHC (OR = 5.48, 95% CI = 2.61–11.50, P < 0.00001; Fig. 2A), and RT-PCR (SMD = 2.28, 95% CI = 0.91–3.64, P = 0.001; Fig. 2B). Seven studies (207 IPAs and 184 NIPAs) and four studies (91 IPAs and 97 NIPAs) showed MMP-2 expression at the protein level and RNA level, respectively. MMP-2 expression was increased in patients with IPAs at the protein level (OR = 3.58, 95% CI = 1.63–7.87, P = 0.001; Fig. 3A), and RNA level (SMD = 3.91, 95% CI = 1.52–6.29, P = 0.001; Fig. 3B). The results of Sensitivity analysis indicated that no single study had a significant influence on the above four-pooled effect sizes (Supplemental Table S2–S5). Subgroup analytical results found that detection methods had no influence on pooled SMD of MMP-9 (test for subgroup differences: I2 = 0%, P = 0.64; Fig. 2B) and MMP-2 (I2 = 0%, P = 0.97; Fig. 3B) at the RNA level.

View Article: PubMed Central - PubMed

ABSTRACT

The extracellular matrix is important for tumor invasion and metastasis. Normal function of the extracellular matrix depends on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The objective of this meta-analysis was to assess the relationship between expression of MMP-9, MMP-2, and TIMP-2 and invasion of pituitary adenomas.

We searched Pubmed, Embase, and the Chinese Biomedical Database up to October 2015. RevMan 5.1 software (Cochrane Collaboration, Copenhagen, Denmark) was used for statistical analysis. We calculated the standardized mean difference (SMD) for data expressed as mean&#8202;&plusmn;&#8202;standard deviation because of the difference in the detection method.

Twenty-four studies (1320 patients) were included. MMP-9 expression was higher in the patients with invasive pituitary adenomas (IPAs) than patients with noninvasive pituitary adenomas (NIPAs) with detection methods of IHC [odds ratio (OR) = 5.48, 95% confidence interval (CI) = 2.61&ndash;11.50, P&#8202;&lt;&#8202;0.00001), and reverse transcriptase-polymerase chain reaction (SMD = 2.28, 95% CI = 0.91&ndash;3.64, P = 0.001). MMP-2 expression was also increased in patients with IPAs at the protein level (OR = 3.58, 95% CI = 1.63&ndash;7.87, P = 0.001), and RNA level (SMD = 3.91, 95% CI = 1.52&ndash;6.29, P = 0.001). Meta-analysis showed that there was no difference in TIMP-2 expression between invasive and NIPAs at the protein level (OR = 0.38, 95% CI = 0.06&ndash;2.26, P = 0.29). MMP-9 expression in prolactinomas and nonfunctioning pituitary adenomas was also no difference (OR = 1.03, 95% CI = 0.48&ndash;2.20, P = 0.95).

The results indicated that MMP-9 and -2 may be correlated with invasiveness of pituitary adenomas, although their relationship with functional status of pituitary adenomas is still not clear. TIMP-2 expression in IPAs needs to be investigated further.

No MeSH data available.


Related in: MedlinePlus