Shahar Tal, Rozovski Uri, Hess Kenneth R, Hossain Anwar, Gumin Joy, Gao Feng, Fuller Gregory N, Goodman Lindsey, Sulman Erik P, Lang Frederick F
Department of Neurosurgery, Unit 442, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
Brain Tumor Center, Unit 442, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
Neuro Oncol. 2017 May 1;19(5):660-668. doi: 10.1093/neuonc/now239.
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.
人骨髓间充质干细胞（hMSCs）已被证明作为胶质瘤相关的hMSCs（GA-hMSCs）以基质细胞的形式存在于人类胶质瘤中，但其生物学作用仍不清楚。由于最近的证据表明GA-hMSCs可驱动肿瘤细胞增殖和干性，我们推测肿瘤中GA-hMSCs比例较高预示着患者预后不良。
我们测定了新诊断的高级别胶质瘤患者中共同表达GA-hMSC标志物CD105+/CD73+/CD90+的细胞百分比，并在3个独立队列中分析了该百分比与总生存期（OS）之间的关联：新鲜手术切除的胶质母细胞瘤标本（队列1，N = 9）、第3代培养的肿瘤标本（队列2，N = 28）以及癌症基因组图谱（TCGA）数据库。
在所有队列中，患者的总生存期与肿瘤中GA-hMSCs的百分比相关。对于队列1，三阳性细胞百分比低的肿瘤患者的中位总生存期为46个月，而三阳性细胞百分比高的肿瘤患者为12个月（风险比[HR]=0.24；95%可信区间：0.02 - 0.5，P = 0.02）。对于队列2，GA-hMSCs百分比低的肿瘤患者的中位总生存期为66个月，而百分比高的肿瘤患者为11个月（HR = 0.38；95%可信区间：0.13 - 0.9，P = 0.04）。在TCGA数据库中，CD105/CD73/CD90共表达水平高和低的患者的中位总生存时间分别为8.4个月和13.1个月（HR = 0.4；95%可信区间：0.1 - 0.88；P = 0.04）。
GA-MSCs的百分比与总生存期呈负相关，提示GA-MSCs在促进胶质瘤侵袭性行为中发挥作用。
