Department of Translational Molecular Medicine, Saint John's Cancer Institute (SJCI) at Providence Saint John's Health Center (SJHC), Santa Monica, CA, 90404, USA.
Department of Genome Sequencing, SJCI at Providence SJHC, Santa Monica, CA, 90404, USA.
Lab Invest. 2022 Jul;102(7):711-721. doi: 10.1038/s41374-021-00720-4. Epub 2022 Jan 10.
Glioblastoma (GBM) is still one of the most commonly diagnosed advanced stage primary brain tumors. Current treatments for patients with primary GBM (pGBM) are often not effective and a significant proportion of the patients with pGBM recur. The effective treatment options for recurrent GBM (rGBM) are limited and survival outcomes are poor. This retrospective multicenter pilot study aims to determine potential cell-free microRNAs (cfmiRs) that identify patients with pGBM and rGBM tumors. 2,083 miRs were assessed using the HTG miRNA whole transcriptome assay (WTA). CfmiRs detection was compared in pre-operative plasma samples from patients with pGBM (n = 32) and rGBM (n = 13) to control plasma samples from normal healthy donors (n = 73). 265 cfmiRs were found differentially expressed in plasma samples from pGBM patients compared to normal healthy donors (FDR < 0.05). Of those 193 miRs were also detected in pGBM tumor tissues (n = 15). Additionally, we found 179 cfmiRs differentially expressed in rGBM, of which 68 cfmiRs were commonly differentially expressed in pGBM. Using Random Forest algorithm, specific cfmiR classifiers were found in the plasma of pGBM, rGBM, and both pGBM and rGBM combined. Two common cfmiR classifiers, miR-3180-3p and miR-5739, were found in all the comparisons. In receiving operating characteristic (ROC) curves analysis for rGBM miR-3180-3p showed a specificity of 87.7% and a sensitivity of 100% (AUC = 98.5%); while miR-5739 had a specificity of 79.5% and sensitivity of 92.3% (AUC = 90.2%). This study demonstrated that plasma samples from pGBM and rGBM patients have specific miR signatures. CfmiR-3180-3p and cfmiR-5739 have potential utility in diagnosing patients with pGBM and rGBM tumors using a minimally invasive blood assay.
胶质母细胞瘤（GBM）仍然是最常见的诊断为晚期原发性脑肿瘤之一。目前对原发性 GBM（pGBM）患者的治疗往往效果不佳，相当一部分 pGBM 患者会复发。复发性 GBM（rGBM）的有效治疗选择有限，生存结局较差。这项回顾性多中心试点研究旨在确定可识别 pGBM 和 rGBM 肿瘤患者的潜在无细胞 microRNAs（cfmiRs）。使用 HTG miRNA 全转录组分析（WTA）评估了 2083 个 miRs。比较了 pGBM（n=32）和 rGBM（n=13）患者术前血浆样本与正常健康供者（n=73）的 cfmiRs 检测结果。与正常健康供者相比，pGBM 患者的血浆样本中发现 265 个 cfmiRs 差异表达（FDR<0.05）。其中 193 个 miRs 在 pGBM 肿瘤组织中也有检测到（n=15）。此外，我们还发现 rGBM 中 179 个 cfmiRs 差异表达，其中 68 个 cfmiRs 在 pGBM 中共同差异表达。使用随机森林算法，在 pGBM、rGBM 以及 pGBM 和 rGBM 合并的血浆中发现了特定的 cfmiR 分类器。在所有比较中，都发现了两个常见的 cfmiR 分类器，miR-3180-3p 和 miR-5739。在 rGBM 的接收者操作特征（ROC）曲线分析中，miR-3180-3p 的特异性为 87.7%，敏感性为 100%（AUC=98.5%）；而 miR-5739 的特异性为 79.5%，敏感性为 92.3%（AUC=90.2%）。这项研究表明，pGBM 和 rGBM 患者的血浆样本具有特定的 miR 特征。cfmiR-3180-3p 和 cfmiR-5739 具有通过微创血液检测诊断 pGBM 和 rGBM 肿瘤患者的潜在效用。
