Abstract
AbstractGliomas are the most common and recalcitrant intracranial tumors, approximately a quarter of which are classified as lower-grade gliomas (WHO II–III). Although the prognosis of lower-grade gliomas (LGGs) is significantly better than that of higher-grade gliomas, as a highly heterogeneous tumor type, the prognosis of LGGs varies greatly based on the molecular diagnosis. IDH wild-type used to be regarded as a dismal prognostic biomarker in LGGs; however, several studies revealed that IDH wild-type LGGs might not always be equivalent to glioblastoma (WHO IV). Hence, we hypothesize that underlying biological events in LGGs can result in different prognosis. In our study, transcriptome profiling was performed in 24 samples of LGG, and the results showed that the expression of phospholipase Cγ1 (PLCG1) was significantly correlated with IDH1/2 status and patients' clinical outcome. Furthermore, the cancer genome atlas (TCGA) and the Chinese glioma genome atlas (CGGA) databases verified that elevated PLCG1 expression was associated with tumor progression and poor survival in LGG patients. Moreover, PLCG1-targeted siRNA dramatically affected the growth, migration and invasiveness of IDH wild-type LGG cell lines. In in vitro and in vivo experiments, the PLC-targeted drug significantly suppressed the tumor growth of IDH wild-type LGG cell lines in vitro and tumors in mouse models. Taken together, our results demonstrated that higher PLCG1 expression was associated with tumor growth and worse prognosis in IDH wild-type LGGs and PLCG1 could serve as a potential therapeutic target for IDH wild-type LGG patients.The mRNA expression levels of phospholipase Cγ1 (PLCG1) are much higher in IDH wild-type (IDHwt) lower-grade gliomas (LGGs) than in that of IDH mutant (IDHmut) LGGs. Higher PLCG1expression in IDHwt LGGs indicates poor clinical outcome. PLCG1 amplification may act as the key mechanism of PLCG1 upregulation. Depletion of PLCG1 expression can inhibits proliferation and invasion of IDHwt LGG cell lines in vitro and in vivo. The PLC inhibitor U73122 may therefore be a potential therapeutical agent for IDHwt LGGs.
Highlights
Glioma is the most common malignant tumor of the central nervous system, with an increasing incidence rate in recent years[1]
Commercial antibodies against PLCG1, beta-actin-HRP and anti-rabbit HRP secondary antibody were obtained from Cell Signaling Technology
In our transcriptome profiling results, we identified 302 upregulated genes and 881 downregulated genes in IDH wild-type (IDHwt) lower-grade gliomas (LGGs) (Fig. 1a)
Summary
Glioma is the most common malignant tumor of the central nervous system, with an increasing incidence rate in recent years[1]. In the recent publications, histological grade and comprehensive molecular assessment were reported to be significantly important for clinical stratification in IDHwt LGGs with molecular features of glioblastoma, especially for TERT promoter mutation status and methylome characteristics[13,14]. Large-scale deep sequencing based on the original specimens from The Cancer Genome Atlas (TCGA) was conducted and stratified IDHwt LGGs into four subtypes: classic-like, mesenchymal-like, LGm6-GBM and PA-like[15]. All these findings indicated that different biological pathways might be involved in IDHwt glioma oncogenesis and malignant transformation, especially transcriptome and posttranscription alterations in IDHwt LGG, which need to be further elucidated.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
