German Cancer Consortium (DKTK) Core-Center, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Heidelberg Ion-Beam Therapy Center (HIT), Divisions of Molecular & Translational Radiation Oncology, Heidelberg University Hospital (UKHD), 69120 Heidelberg, Germany.
Int J Mol Sci. 2021 Mar 15;22(6):2960. doi: 10.3390/ijms22062960.
MicroRNAs (miRs) are non-coding master regulators of transcriptome that could act as tumor suppressors (TSs) or oncogenes (oncomiRs). We aimed to systematically investigate the relevance of miRs as prognostic biomarkers in primary glioblastoma multiforme (GBM) treated with postoperative radio(chemo)therapy (PORT). For hypothesis generation, tumor miR expression by Agilent 8x15K human microRNA microarrays and survival data from 482 GBM patients of The Cancer Genome Atlas (TCGA cohort) were analyzed using Cox-PH models. Expression of candidate miRs with prognostic relevance (miR-221/222; miR-17-5p, miR-18a, miR-19b) was validated by qRT-PCR using Taqman technology on an independent validation cohort of GBM patients ( = 109) treated at Heidelberg University Hospital (HD cohort). In TCGA, 50 miRs showed significant association with survival. Among the top ranked prognostic miRs were members of the two miR families miR-221/222 and miR-17-92. Loss of miR-221/222 was correlated with improved prognosis in both cohorts (TCGA, HD) and was an independent prognostic marker in a multivariate analysis considering demographic characteristics (age, sex, Karnofsky performance index (KPI)), molecular markers (O-6-methylguanine-DNA methyltransferase (MGMT) methylation, IDH mutation status) and PORT as co-variables. The prognostic value of miR-17-92 family members was ambiguous and in part contradictory by direct comparison of the two cohorts, thus warranting further validation in larger prospective trials.
微小 RNA（miRs）是转录组的非编码主调控因子，可作为肿瘤抑制因子（TSs）或癌基因（oncomiRs）发挥作用。我们旨在系统研究 miR 在接受术后放化疗（PORT）治疗的原发性多形性胶质母细胞瘤（GBM）中作为预后生物标志物的相关性。为了产生假说，我们使用 Cox-PH 模型分析了来自 482 名 GBM 患者的肿瘤 miR 表达（来自 TCGA 队列的 Agilent 8x15K 人类 microRNA 微阵列）和生存数据。使用 Taqman 技术通过 qRT-PCR 对具有预后相关性的候选 miR（miR-221/222；miR-17-5p、miR-18a、miR-19b）进行了验证，该验证队列由在海德堡大学医院（HD 队列）接受治疗的独立 GBM 患者（n = 109）组成。在 TCGA 中，有 50 个 miRs 与生存显著相关。在排名最高的预后 miR 中，有两个 miR 家族的成员 miR-221/222 和 miR-17-92。在两个队列（TCGA、HD）中，miR-221/222 的丢失与预后改善相关，并且在考虑人口统计学特征（年龄、性别、卡诺夫斯基表现指数（KPI））、分子标志物（O-6-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）甲基化、IDH 突变状态）和 PORT 作为协变量的多变量分析中，是一个独立的预后标志物。miR-17-92 家族成员的预后价值通过两个队列的直接比较存在分歧和矛盾，因此需要在更大的前瞻性试验中进一步验证。
Zotero 插件
