Percentage of mesenchymal stem cells in high-grade glioma tumor samples correlates with patient survival
Percentage of mesenchymal stem cells in high-grade glioma tumor samples correlates with patient survival
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DOI：
10.1093/neuonc/now239
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发表时间：
2017-05-01
期刊：
影响因子：
15.9
通讯作者：
Lang, Frederick F.
中科院分区：
文献类型：
--
作者：
Shahar, Tal;Rozovski, Uri;Lang, Frederick F.
人间充质干细胞（human mesenchymal stem cells，hMSCs）作为胶质瘤相关的间充质干细胞（glioma-associated hMSCs，GA-hMSCs）存在于人脑胶质瘤中，但其生物学作用尚不清楚。由于最近的证据表明GA-hMSC驱动肿瘤细胞增殖和干细胞，我们假设肿瘤中较高比例的GA-hMSC预示着患者预后不良。我们确定了新诊断的高级别胶质瘤患者中共表达GA-hMSC标志物CD 105 +/CD 73 +/CD 90+的细胞百分比，并分析了3个独立队列中该百分比与总生存期（OS）之间的关系：新鲜的手术胶质母细胞瘤标本（组1，N = 9）、第3代培养的肿瘤标本（组2，N = 28）和癌症基因组图谱（TCGA）数据库。对于队列1，三重阳性细胞百分比低的肿瘤患者的中位OS为46个月，三重阳性细胞百分比高的肿瘤患者的中位OS为12个月（风险比[HR] = 0.24; 95% CI：0.02-0.5，P = 0.02）。对于队列2，具有低百分比GA-hMSC的肿瘤的患者的中位OS为66个月，并且对于具有高百分比的肿瘤，其为11个月（HR = 0.38; 95%CI：0.13-0.9，P = 0.04）。在TCGA数据库中，CD 105/CD 73/CD 90高表达和低表达患者的中位OS时间分别为8.4个月和13.1个月（HR = 0.4; 95%CI：0.1-0.88; P = 0.04），GA-MSCs的百分比与OS呈负相关，提示GA-MSCs在促进胶质瘤侵袭行为中的作用。
Human mesenchymal stem cells (hMSCs) have been shown to reside as stromal cells in human gliomas as glioma-associated hMSCs (GA-hMSCs), but their biological role remains unclear. Because recent evidence indicates that GA-hMSCs drive tumor cell proliferation and stemness, we hypothesized that a higher percentage of GA-hMSCs in tumors predicts poor patient prognosis.We determined the percentage of cells coexpressing GA-hMSC markers CD105+/CD73+/CD90+ from patients with newly diagnosed high-grade glioma and analyzed the association between this percentage and overall survival (OS) in 3 independent cohorts: fresh surgical glioblastoma specimens (cohort 1, N = 9), cultured tumor specimens at passage 3 (cohort 2, N = 28), and The Cancer Genome Atlas (TCGA) database.In all cohorts, patient OS correlated with the percentages of GA-hMSCs in tumors. For cohort 1, the median OS of patients with tumors with a low percentage of triple-positive cells was 46 months, and for tumors with a high percentage of triple-positive cells, it was 12 months (hazard ratio [HR] = 0.24; 95% CI: 0.02-0.5, P = .02). For cohort 2, the median OS of patients with tumors with a low percentage of GA-hMSCs was 66 months, and for tumors with a high percentage, it was 11 months (HR = 0.38; 95% CI: 0.13-0.9, P = .04). In the database of TCGA, the median OS times in patients with high and low coexpression levels of CD105/CD73/CD90 were 8.4 months and 13.1 months (HR = 0.4; 95% CI: 0.1-0.88; P = .04), respectively.The percentage of GA-MSCs inversely correlates with OS, suggesting a role for GA-MSCs in promoting aggressive behavior of gliomas.