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ADAM9 Expression Is Associate with Glioma Tumor Grade and Histological Type, and Acts as a Prognostic Factor in Lower-Grade Gliomas

View Article: PubMed Central - PubMed

ABSTRACT

The A disintegrin and metalloproteinase 9 (ADAM9) protein has been suggested to promote carcinoma invasion and appears to be overexpressed in various human cancers. However, its role has rarely been investigated in gliomas and, thus, in the current study we have evaluated ADAM9 expression in gliomas and examined the relevance of its expression in the prognosis of glioma patients. Clinical characteristics, RNA sequence data, and the case follow-ups were reviewed for 303 patients who had histological, confirmed gliomas. The ADAM9 expression between lower-grade glioma (LGG) and glioblastoma (GBM) patients was compared and its association with progression-free survival (PFS) and overall survival (OS) was assessed to evaluate its prognostic value. Our data suggested that GBM patients had significantly higher expression of ADAM9 in comparison to LGG patients (p < 0.001, t-test). In addition, among the LGG patients, aggressive astrocytic tumors displayed significantly higher ADAM9 expression than oligodendroglial tumors (p < 0.001, t-test). Moreover, high ADAM9 expression also correlated with poor clinical outcome (p < 0.001 and p < 0.001, log-rank test, for PFS and OS, respectively) in LGG patients. Further, multivariate analysis suggested ADAM9 expression to be an independent marker of poor survival (p = 0.002 and p = 0.003, for PFS and OS, respectively). These results suggest that ADAM9 mRNA expression is associated with tumor grade and histological type in gliomas and can serve as an independent prognostic factor, specifically in LGG patients.

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Comparison of ADAM9 mRNA expression levels between LGG and GBM tumor samples. The LGG tumor samples displayed an average of 4.098 ± 2.132 TPM units of ADAM9 mRNA expression, while GBM tumor samples displayed an average of 8.139 ± 4.922 TPM units of ADAM9 mRNA expression. The difference was significant between the two subtypes, p < 0.001, t-test. TPM, transcripts per million; LGG, lower-grade glioma; GBM, glioblastoma.
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ijms-17-01276-f001: Comparison of ADAM9 mRNA expression levels between LGG and GBM tumor samples. The LGG tumor samples displayed an average of 4.098 ± 2.132 TPM units of ADAM9 mRNA expression, while GBM tumor samples displayed an average of 8.139 ± 4.922 TPM units of ADAM9 mRNA expression. The difference was significant between the two subtypes, p < 0.001, t-test. TPM, transcripts per million; LGG, lower-grade glioma; GBM, glioblastoma.

Mentions: The gene expressions of 22 members of the ADAM family were compared between patients with different grades of gliomas. Among these, 14 genes showed a statistically significant difference in the mRNA expression between different grades of gliomas, including ADAM9 (Supplementary Table S1). ADAM9 mRNA expression was higher in GBM patient samples (8.139 ± 4.922 transcripts per million, TPM, units) as compared to LGG patients (4.098 ± 2.132 TPM units), and this difference was significant (p < 0.001, t-test, Figure 1). Next, the potential correlation between ADAM9 expression and clinical characteristics was examined using Chi-square analysis (Table 2). We observed a significant association between ADAM9 expression and histological type in patients with lower-grade gliomas (p < 0.001, Chi-square test). Further analysis of the association between ADAM9 expression and different histological types of LGG revealed that astrocytic tumors had significantly higher expression than oligodendroglial tumors (6.051 ± 0.460 vs. 4.228 ± 0.231, p < 0.001, t-test, Figure 2A). Additionally, we also found that the ADAM9 expression level was significantly associated with 1p/19q co-deletion in patients with lower-grade gliomas (p = 0.002, Chi-square test). Student’s t-test, used to determine this association, more specifically showed that ADAM9 expression was significantly lower in LGG patients with the 1p/19q co-deletion.


ADAM9 Expression Is Associate with Glioma Tumor Grade and Histological Type, and Acts as a Prognostic Factor in Lower-Grade Gliomas
Comparison of ADAM9 mRNA expression levels between LGG and GBM tumor samples. The LGG tumor samples displayed an average of 4.098 ± 2.132 TPM units of ADAM9 mRNA expression, while GBM tumor samples displayed an average of 8.139 ± 4.922 TPM units of ADAM9 mRNA expression. The difference was significant between the two subtypes, p < 0.001, t-test. TPM, transcripts per million; LGG, lower-grade glioma; GBM, glioblastoma.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037653&req=5

ijms-17-01276-f001: Comparison of ADAM9 mRNA expression levels between LGG and GBM tumor samples. The LGG tumor samples displayed an average of 4.098 ± 2.132 TPM units of ADAM9 mRNA expression, while GBM tumor samples displayed an average of 8.139 ± 4.922 TPM units of ADAM9 mRNA expression. The difference was significant between the two subtypes, p < 0.001, t-test. TPM, transcripts per million; LGG, lower-grade glioma; GBM, glioblastoma.
Mentions: The gene expressions of 22 members of the ADAM family were compared between patients with different grades of gliomas. Among these, 14 genes showed a statistically significant difference in the mRNA expression between different grades of gliomas, including ADAM9 (Supplementary Table S1). ADAM9 mRNA expression was higher in GBM patient samples (8.139 ± 4.922 transcripts per million, TPM, units) as compared to LGG patients (4.098 ± 2.132 TPM units), and this difference was significant (p < 0.001, t-test, Figure 1). Next, the potential correlation between ADAM9 expression and clinical characteristics was examined using Chi-square analysis (Table 2). We observed a significant association between ADAM9 expression and histological type in patients with lower-grade gliomas (p < 0.001, Chi-square test). Further analysis of the association between ADAM9 expression and different histological types of LGG revealed that astrocytic tumors had significantly higher expression than oligodendroglial tumors (6.051 ± 0.460 vs. 4.228 ± 0.231, p < 0.001, t-test, Figure 2A). Additionally, we also found that the ADAM9 expression level was significantly associated with 1p/19q co-deletion in patients with lower-grade gliomas (p = 0.002, Chi-square test). Student’s t-test, used to determine this association, more specifically showed that ADAM9 expression was significantly lower in LGG patients with the 1p/19q co-deletion.

View Article: PubMed Central - PubMed

ABSTRACT

The A disintegrin and metalloproteinase 9 (ADAM9) protein has been suggested to promote carcinoma invasion and appears to be overexpressed in various human cancers. However, its role has rarely been investigated in gliomas and, thus, in the current study we have evaluated ADAM9 expression in gliomas and examined the relevance of its expression in the prognosis of glioma patients. Clinical characteristics, RNA sequence data, and the case follow-ups were reviewed for 303 patients who had histological, confirmed gliomas. The ADAM9 expression between lower-grade glioma (LGG) and glioblastoma (GBM) patients was compared and its association with progression-free survival (PFS) and overall survival (OS) was assessed to evaluate its prognostic value. Our data suggested that GBM patients had significantly higher expression of ADAM9 in comparison to LGG patients (p &lt; 0.001, t-test). In addition, among the LGG patients, aggressive astrocytic tumors displayed significantly higher ADAM9 expression than oligodendroglial tumors (p &lt; 0.001, t-test). Moreover, high ADAM9 expression also correlated with poor clinical outcome (p &lt; 0.001 and p &lt; 0.001, log-rank test, for PFS and OS, respectively) in LGG patients. Further, multivariate analysis suggested ADAM9 expression to be an independent marker of poor survival (p = 0.002 and p = 0.003, for PFS and OS, respectively). These results suggest that ADAM9 mRNA expression is associated with tumor grade and histological type in gliomas and can serve as an independent prognostic factor, specifically in LGG patients.

No MeSH data available.


Related in: MedlinePlus