Promising Prognosis Marker Candidates on the Status of Epithelial–Mesenchymal Transition and Glioma Stem Cells in Glioblastoma

Abstract

Multivariable analyses of global expression profiling are valid indicators of the prognosis of various diseases including brain cancers. To identify the candidates for markers of prognosis of glioblastoma, we performed multivariable analyses on the status of epithelial (EPI)-mesenchymal (MES) transition (EMT), glioma (GLI) stem cells (GSCs), molecular target therapy (MTT), and potential glioma biomarkers (PGBs) using the expression data and clinical information from patients. Random forest survival and Cox proportional hazards regression analyses indicated significant variable values for DSG3, CLDN1, CDH11, FN1, HDAC3/7, PTEN, L1CAM, OLIG2, TIMP4, IGFBP2, and GFAP. The analyses also comprised prognosis prediction formulae that could distinguish between the survival curves of the glioblastoma patients. In addition to the genes mentioned above, HDAC1, FLT1, EGFR, MGMT, PGF, STAT3, SIRT1, and GADD45A constituted complex genetic interaction networks. The calculated status scores obtained by principal component analysis indicated that GLI genes covered the status of EPI, GSC, and MTT-related genes. Moreover, survival tree analyses indicated that MES high , MES high GLI low , GSC high GLI low , MES high MTT low , and PGB high showed poor prognoses and MES middle , GSC low , and PGB low showed good prognoses, suggesting that enhanced EMT and GSC are associated with poor survival and that lower expression of EPI markers and the pre-stages of EMT are relatively less malignant in glioblastoma. These results demonstrate that the assessment of EMT and GSC enables the prediction of the prognosis of glioblastoma that would help develop novel therapeutics and de novo marker candidates for the prognoses of glioblastoma.

Correlation and Mechanism Study of Multivoxel 1H-MRS Parameters, Cho / Cr and CHKA

“…Therefore, we speculate that there may be some relationship between CHKA and glioma stem cells, Katharina Koch. Our results suggest that CHKA is an important regulator of EMT in glioblastocytes, and EMT, as a key transformation pathway for malignant tumor cells to acquire invasiveness, may be an important reason for therapeutic resistance and tumor recurrence of glioma stem cells [38].Our experimental results also show that CHKA is related to glioma stem cells and its inhibitor MN58b can slow down the progress of EMT,these are consistent with our conjecture.…”

Ethyl pyruvate inhibits glioblastoma cells migration and invasion through modulation of NF-κB and ERK-mediated EMT

“…It is a key link in tumor cell invasion and metastasis and is closely related to the occurrence and development of tumors (Kalluri & Weinberg, 2009). Nowadays, a large number of studies have proved that EMT or EMT(-like) plays an important role not only in the in-situ invasion and distant metastasis of breast cancer, cervical cancer, gastric cancer and some other tumors (Jiang et al, 2019;Liu et al, 2017;Nath et al, 2019;Nishizuka, Komada & Imagawa, 2019;Sun et al, 2018;Yilmaz & Christofori, 2009), but also in the invasive growth of malignant glioma (Iser et al, 2017;Mikheeva et al, 2010;Takashima, Kawaguchi & Yamanaka, 2019). In the EMT process, the cell polarity disappears, the adhesion weakens and it morphologically transforms from epithelial cells to mesenchymal cells.…”

Single-Cell Mechanophenotyping in Microfluidics to Evaluate Behavior of U87 Glioma Cells

“…Hence, it is an extremely dynamic, hierarchical microenvironment [ 5 ]. Moreover, highly activated epithelial-mesenchymal transition (EMT) and existence of glioma stem-like cells (GSCs) drive resistance and relapse in therapy [ 6 , 7 , 8 ]. Tremendously increased aggressiveness and invasiveness of GBM requires adequate single-cell tools to avoid masking rare cells and to allow quantifying heterogeneity according to morphologic, phenotypic, and functional properties of glioma cells in a population.…”