Abstract
Glioma is the most malignant brain tumor and glioblastoma (GBM) is the most aggressive type. The involvement of N-myc (and STAT) interactor (NMI) in tumorigenesis was sporadically reported but far from elucidation. This study aims to investigate roles of NMI in human glioma. Three independent cohorts, the Chinese tissue microarray (TMA) cohort (N = 209), the Repository for Molecular Brain Neoplasia Data (Rembrandt) cohort (N = 371) and The Cancer Genome Atlas (TCGA) cohort (N = 528 or 396) were employed. Transcriptional or protein levels of NMI expression were significantly increased according to tumor grade in all three cohorts. High expression of NMI predicted significantly unfavorable clinical outcome for GBM patients, which was further determined as an independent prognostic factor. Additionally, expression and prognostic value of NMI were associated with molecular features of GBM including PTEN deletion and EGFR amplification in TCGA cohort. Furthermore, overexpression or depletion of NMI revealed its regulation on G1/S progression and cell proliferation (both in vitro and in vivo), and this effect was partially dependent on STAT1, which interacted with and was regulated by NMI. These data demonstrate that NMI may serve as a novel prognostic biomarker and a potential therapeutic target for glioblastoma.
Highlights
Glioma, accounting for approximately 30% of all primary brain and central nervous system (CNS) tumors and 80% of malignant primary brain and CNS tumors [1], is often fast growing with poor prognosis for the patients
We found that N-myc (and STAT) interactor (NMI) was mainly expressed in cytoplasm of cells
Total RNA was extracted from a subset of 42 human glioma specimens (11 diffuse astrocytomas, 10 anaplastic astrocytomas and 21 glioblastomas) and 10 controls randomly selected from this cohort and subjected to real-time quantitative RT-PCR assays
Summary
Glioma, accounting for approximately 30% of all primary brain and central nervous system (CNS) tumors and 80% of malignant primary brain and CNS tumors [1], is often fast growing with poor prognosis for the patients. Substantial efforts have been made in the identification of molecular subtypes [13, 14] and biomarkers associated with GBM patients’ survival [15,16,17], to better understand the pathogenesis of GBM Several public resources, such as the Repository of Molecular Brain Neoplasia Data (Rembrandt) database [18] and The Cancer Genome Atlas (TCGA) network [19] have provided insight into the molecular carcinogenesis of GBM, affording opportunities for researchers to correlate gene expression with multidimensional clinical and molecular features of patients [15, 16, 20,21,22]. Uncovering new molecular targets and prognostic factors, and revealing the correlation of their expression with molecular features of GBM, may provide chances to improve the clinical outcome of GBM patients
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