Abstract
Introduction: Secretogranin III (SCG3) physiologically participates in neurotransmitter storage/transport and is widely expressed in neuroendocrine tumors. However, there is no report on SCG3 protein expression in gliomas. Methods: The method of immunohistochemical staining on a glioma tissue microarray was utilized to detect SCG3 protein expression and investigate the correlations of its expression with clinicopathological and genetic features in gliomas. The RNA-seq data of SCG3 in The Cancer Genome Atlas database was exploited to explore these correlations at the transcriptional level. Results: There were 57.5% (130/226) glioma cases having SCG3 cytoplasmic staining in the tissue microarray. SCG3 expression inversely correlated with malignancy grade at both transcriptional and protein levels. The highest level was observed in oligodendroglial tumors, especially in oligodendrogliomas (ODs) with IDH-mutation/1p19q-codeletion. The lowest SCG3 expression was observed in glioblastomas (GBMs), especially in the mesenchymal subtype. Nearly a half of GBM cases (44.4%, 64/144) had any discernible SCG3 staining, and were defined as SCG3-positive by the microarray study. SCG3-positive GBM cases exhibited improved overall survival as compared with the SCG3-negative cases (29.3 vs. 14.5 months; Hazard ratio, 0.364; 95% CI, 0.216–0.612; p < 0.001). A multivariate Cox regression analysis also revealed SCG3 positivity as an independent favorable prognosticator in GBM patients. Conclusion: SCG3 protein expression inversely correlates with glioma malignancy and predicts favorable outcomes in GBM patients.
Highlights
Secretogranin III (SCG3) physiologically participates in neurotransmitter storage/transport and is widely expressed in neuroendocrine tumors
Isocitrate dehydrogenase (IDH) mutations are indicative of favorable outcomes in all glioma patients [3], whereas telomerase reverse transcriptase promoter (TERTp) mutations are associated with poor prognosis in patients with glioblastoma (GBM), a grade IV glioma [4]
RNA-seq data pertaining to secretogranin III (SCG3) in gliomas (160 GBMs and 515 Grade II/ III gliomas) and the associated clinical and molecular information were extracted from The Cancer Genome Atlas (TCGA; http://cancergenome.nih.gov/) for analysis
Summary
Secretogranin III (SCG3) physiologically participates in neurotransmitter storage/transport and is widely expressed in neuroendocrine tumors. Glioma is a molecularly heterogeneous brain malignancy associated with distinct therapy responses and diverse clinical outcomes [1, 2]. Molecular classification optimizes treatment selection and eventually improves prognosis of glioma patients. Several markers have been widely used in clinical practice to guide accurate diagnosis and precise treatment of glioma patients. Isocitrate dehydrogenase (IDH) mutations are indicative of favorable outcomes in all glioma patients [3], whereas telomerase reverse transcriptase promoter (TERTp) mutations are associated with poor prognosis in patients with glioblastoma (GBM), a grade IV glioma [4]. Each subtype has unique genetic aberrations and is associated with distinct clinical outcomes [6]
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