Monopolar Spindle 1 Kinase (MPS1/TTK) mRNA Expression is Associated with Earlier Development of Clinical Symptoms, Tumor Aggressiveness and Survival of Glioma Patients

被引：10

作者：

Kessler, Almuth F. ^{[1
]}

Feldheim, Jonas ^{[1
]}

Schmitt, Dominik ^{[1
]}

Feldheim, Julia J. ^{[1
]}

Monoranu, Camelia M. ^{[2
]}

Ernestus, Ralf-Ingo ^{[1
]}

Loehr, Mario ^{[1
]}

Hagemann, Carsten ^{[1
]}

机构：

[1] Univ Wurzburg, Dept Neurosurg, Tumorbiol Lab, Josef Schneider Str 11, D-97080 Wurzburg, Germany

[2] Univ Wurzburg, Dept Neuropathol, Intsitute Pathol, Josef Schneider Str 2, D-97080 Wurzburg, Germany

来源：

BIOMEDICINES | 2020年 / 8卷 / 07期

关键词：

glioblastoma multiforme; low-grade glioma; astrocytoma; recurrence; multifocal growth; mRNA expression; MPS1; TTK; therapy; PILOCYTIC ASTROCYTOMA; TREATING FIELDS; GLIOBLASTOMA; MULTICENTER; PATHOLOGY; CLASSIFICATION; BEVACIZUMAB; CHECKPOINT; NECROSIS;

D O I：

10.3390/biomedicines8070192

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Inhibition of the protein kinase MPS1, a mitotic spindle-checkpoint regulator, reinforces the effects of multiple therapies against glioblastoma multiforme (GBM) in experimental settings. We analyzedMPS1mRNA-expression in gliomas WHO grade II, III and in clinical subgroups of GBM. Data were obtained by qPCR analysis of tumor and healthy brain specimens and correlated with the patients' clinical data.MPS1was overexpressed in all gliomas on an mRNA level (ANOVA,p< 0.01) and correlated with tumor aggressiveness. We explain previously published conflicting results on survival: highMPS1was associated with poorer long term survival when all gliomas were analyzed combined in one group (Cox regression: t < 24 months,p= 0.009, Hazard ratio: 8.0, 95% CI: 1.7-38.4), with poorer survival solely in low-grade gliomas (LogRank:p= 0.02, Cox regression:p= 0.06, Hazard-Ratio: 8.0, 95% CI: 0.9-66.7), but not in GBM (LogRank:p> 0.05). This might be due to their lower tumor volume at the therapy start. GBM patients with highMPS1mRNA-expression developed clinical symptoms at an earlier stage. This, however, did not benefit their overall survival, most likely due to the more aggressive tumor growth. SinceMPS1mRNA-expression in gliomas was enhanced with increasing tumor aggressiveness, patients with the worst outcome might benefit best from a treatment directed against MPS1.

引用

页数：13