Hagemann Carsten, Neuhaus Nikolas, Dahlmann Mathias, Kessler Almuth F, Kobelt Dennis, Herrmann Pia, Eyrich Matthias, Freitag Benjamin, Linsenmann Thomas, Monoranu Camelia M, Ernestus Ralf-Ingo, Löhr Mario, Stein Ulrike
Tumorbiology Laboratory, Department of Neurosurgery, University of Würzburg, Josef-Schneider-Str. 11, D-97080 Würzburg, Germany.
Experimental and Clinical Research Center, Charité Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, D-13125 Berlin, Germany.
Cancers (Basel). 2019 Jun 13;11(6):825. doi: 10.3390/cancers11060825.
Glioblastoma multiforme is the most aggressive primary brain tumor of adults, but lacks reliable and liquid biomarkers. We evaluated circulating plasma transcripts of metastasis-associated in colon cancer-1 (MACC1), a prognostic biomarker for solid cancer entities, for prediction of clinical outcome and therapy response in glioblastomas. MACC1 transcripts were significantly higher in patients compared to controls. Low MACC1 levels clustered together with other prognostically favorable markers. It was associated with patients' prognosis in conjunction with the isocitrate dehydrogenase (IDH) mutation status: IDH1 R132H mutation and low MACC1 was most favorable (median overall survival (OS) not yet reached), IDH1 wildtype and high MACC1 was worst (median OS 8.1 months), while IDH1 wildtype and low MACC1 was intermediate (median OS 9.1 months). No patients displayed IDH1 R132H mutation and high MACC1. Patients with low MACC1 levels receiving standard therapy survived longer (median OS 22.6 months) than patients with high MACC1 levels (median OS 8.1 months). Patients not receiving the standard regimen showed the worst prognosis, independent of MACC1 levels (low: 6.8 months, high: 4.4 months). Addition of circulating MACC1 transcript levels to the existing prognostic workup may improve the accuracy of outcome prediction and help define more precise risk categories of glioblastoma patients.
多形性胶质母细胞瘤是成人中最具侵袭性的原发性脑肿瘤，但缺乏可靠的和可流动的生物标志物。我们评估了结肠癌转移相关蛋白1（MACC1）的循环血浆转录本，MACC1是实体癌的一种预后生物标志物，用于预测胶质母细胞瘤的临床结局和治疗反应。与对照组相比，患者的MACC1转录本显著更高。低MACC1水平与其他预后良好的标志物聚集在一起。它与患者的预后以及异柠檬酸脱氢酶（IDH）突变状态相关：IDH1 R132H突变且MACC1低是最有利的（总生存期（OS）中位数尚未达到），IDH1野生型且MACC1高是最差的（OS中位数8.1个月），而IDH1野生型且MACC1低处于中间水平（OS中位数9.1个月）。没有患者表现出IDH1 R132H突变且MACC1高。接受标准治疗的MACC1水平低的患者比MACC1水平高的患者存活时间更长（OS中位数22.6个月 vs. 8.1个月）。未接受标准治疗方案的患者预后最差，与MACC1水平无关（低：6.8个月，高：4.4个月）。将循环MACC1转录本水平纳入现有的预后评估可能会提高结局预测的准确性，并有助于更精确地定义胶质母细胞瘤患者的风险类别。
