Department of Neurosurgery, the Second Affiliated Hospital of Shandong First Medical University, #706 Taishan Street, Tai'an, Shandong, 271000, China.
Department of Neurointensive Care Unit, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, China.
Ir J Med Sci. 2024 Apr;193(2):585-593. doi: 10.1007/s11845-023-03500-9. Epub 2023 Aug 24.
Glioblastoma(GBM) is the most common primary tumor of the central nervous system with an extremely dismal prognosis. Many progresses have been made such as the discovery of new molecular biomarkers and target drugs especially IDH inhibitors. However, GBM prognosis is still poor, which requires more biomarkers and drug targets for more precision classification and treatment.
Potential prognostic biomarkers of GBM were screened by TCGA database, and ectopic up-regulation of PARP14 was identified. Expression and clinical significance of PARP14 were detected in our GBM cohort consisting of 143 patients with gross total surgical resection. Related genes with PARP14 were further screened and identified by in silico analysis and in vitro experiments. The expression and prognostic significance of SAMD9 and SAMD9L were verified with IHC and survival analysis in our cohort.
PARP14 was up-regulated in GBM compared with non-tumor adjacent tissues. PARP14 correlated with poor prognosis and can be regarded as an independent prognostic biomarker of GBM. PARP14 expression was positively associated with SAMD9 and SAMD9L in GBM. In GBM cells, PARP14 could increase the expression of SAMD9 and SAMD9L. SAMD9 and SAMD9L were highly expressed in high-PARP14 subset and were both prognostic biomarkers of GBM. Moreover, PARP14 increased GBM proliferation by inducing SAMD9 and SAMD9L expression.
PARP14, SAMD9, and SAMD9L are prognostic biomarkers of GBM predicting poor prognosis. PARP14 promotes GBM cell proliferation by inducing SAMD9 and SAMD9L expression. Our results indicate that PARP14/SAMD9/SAMD9L are prognostic biomarkers and potential drug targets of GBM.
胶质母细胞瘤（GBM）是中枢神经系统最常见的原发性肿瘤，预后极差。随着新的分子生物标志物和靶向药物的发现，尤其是 IDH 抑制剂的发现，已经取得了许多进展。然而，GBM 的预后仍然很差，这需要更多的生物标志物和药物靶点，以进行更精确的分类和治疗。
通过 TCGA 数据库筛选 GBM 的潜在预后生物标志物，鉴定出 PARP14 的异位过表达。在由 143 例完全手术切除的 GBM 患者组成的我们的 GBM 队列中，检测了 PARP14 的表达和临床意义。通过计算机分析和体外实验进一步筛选和鉴定与 PARP14 相关的基因。在我们的队列中，通过 IHC 和生存分析验证了 SAMD9 和 SAMD9L 的表达和预后意义。
与非肿瘤邻近组织相比，PARP14 在 GBM 中上调。PARP14 与不良预后相关，可作为 GBM 的独立预后生物标志物。PARP14 在 GBM 中的表达与 SAMD9 和 SAMD9L 呈正相关。在 GBM 细胞中，PARP14 可增加 SAMD9 和 SAMD9L 的表达。SAMD9 和 SAMD9L 在高 PARP14 亚组中高表达，均为 GBM 的预后生物标志物。此外，PARP14 通过诱导 SAMD9 和 SAMD9L 表达来增加 GBM 的增殖。
PARP14、SAMD9 和 SAMD9L 是预测 GBM 不良预后的预后生物标志物。PARP14 通过诱导 SAMD9 和 SAMD9L 表达促进 GBM 细胞增殖。我们的研究结果表明，PARP14/SAMD9/SAMD9L 是 GBM 的预后生物标志物和潜在的药物靶点。
