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

Xing Fan,Li Liu,Xing Liu,Yongheng Wang,Hui Qiao,Shengyu Fang,Sen Yang,Yinyan Wang,Chuanbao Zhang,Zenghui Qian,Tao Jiang

doi:10.3390/ijms17091276

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.

Highlights

Gliomas are the most common and aggressive primary brain tumors in adults and account for over 70% of the total cases [1,2]
The1574LGG patients4167with low 0A.6-D86AM9 expr13e16ssion were o4b72served to0h.2-a5v3 e a bette1rp/s1u9rqvciov-adleltehtiaonn those wit2h5 high ADAM99 expressio0n.0.02In contrast0, no significant2 difference0s.49w6ere obsNeorv1pe/d19wq citoh-derleestipoenct to eit4h7er progression-free survival (PFS) or OS61in GBM pa-tients, base5d3 on ADAM953expression l-evels (p = 0.994 and 0.656, log-rank test, PFS a* nRdesuOltSs,ofreCshpi-esqcutiavreeltyes,t.Figure 3C,D). This result indicated that A disintegrin and metalloproteinase 9 (ADAM9) expression can serve as a potential prognostic factor for at least lower-grade glioma (LGG) patients
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Summary

Introduction

Gliomas are the most common and aggressive primary brain tumors in adults and account for over 70% of the total cases [1,2]. In recent decades, clinicians and scientists have started to pay more attention to identifying specific tumor-related molecular markers, which in concert with pathological classification can be used for the designing of individualized treatments [6,7] These types of scientific efforts have recently led to substantial progress and different tumor-specific molecular changes, such as isocitrate dehydrogenase 1 (IDH1) mutation [8], 1p/19q co-deletion [9], O6-methylguanine DNA methyltransferase promoter methylation [10], telomerase reverse transcriptase promoter mutation [11], epithelial growth factor receptor amplification [12] and a few others, have been identified as predictive and prognostic indicators and/or therapeutic targets for glioma patients. The identification of new biomarkers can provide more options to confidently predict the survival and/or response of individualized treatment therapy in gliomas patients

Methods

Results

Conclusion