Department of Neurosurgery/China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, China.
Pathol Oncol Res. 2021 Feb 26;27:594931. doi: 10.3389/pore.2021.594931. eCollection 2021.
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. 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. 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; < 0.001). A multivariate Cox regression analysis also revealed SCG3 positivity as an independent favorable prognosticator in GBM patients. SCG3 protein expression inversely correlates with glioma malignancy and predicts favorable outcomes in GBM patients.
分泌颗粒蛋白 III（SCG3）在生理上参与神经递质的储存/转运，广泛表达于神经内分泌肿瘤中。然而，目前尚无关于 SCG3 蛋白在神经胶质瘤中表达的报道。本研究采用免疫组织化学染色方法检测胶质瘤组织芯片中 SCG3 蛋白的表达，并探讨其表达与神经胶质瘤临床病理和遗传学特征的相关性。利用癌症基因组图谱数据库中的 SCG3 RNA-seq 数据从转录水平探索这些相关性。在组织微阵列中，有 57.5%（130/226）的神经胶质瘤病例存在 SCG3 细胞质染色。SCG3 的表达在转录和蛋白水平上均与恶性程度呈负相关。在少突胶质细胞瘤中观察到最高水平，尤其是在 IDH 突变/1p19q 共缺失的少突胶质细胞瘤中。SCG3 表达最低的是胶质母细胞瘤（GBM），特别是间充质亚型。近一半的 GBM 病例（44.4%，64/144）有明显的 SCG3 染色，根据微阵列研究被定义为 SCG3 阳性。与 SCG3 阴性病例相比，SCG3 阳性 GBM 病例的总生存期得到改善（29.3 与 14.5 个月；风险比，0.364；95%CI，0.216-0.612；<0.001）。多因素 Cox 回归分析也表明，SCG3 阳性是 GBM 患者的独立预后良好因素。SCG3 蛋白表达与神经胶质瘤恶性程度呈负相关，可预测 GBM 患者的良好预后。
