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A Functional Approach for Searching Biomarkers of Glioma.

Kopylov А, Chemistry Department, M.V. Lomonosov Moscow State University, Ltd Apta-pharm, Russia; Pasynkova К, Institute of Gene Biology, RAS, Ltd Apta-pharm, Russia; Pustogarov N, Institute of Gene Biology, RAS, Ltd Apta-pharm, Russia; Pavlova G, Institute of Gene Biology, RAS, Ltd Apta-pharm, Russia


Modern trends in developing biomarker for tumors, including gliomas, have been bifurcated into following main directions. The first one is studying differential expression of genes in tumors versus corresponding normal tissues yielding the Big Data. The second is detailed expert studying of expression of particular genes selected according to their presumed function in glioblastoma multiform (GBM) development and malignancy.
Neural cancer stem cells (NCSCs) or neural/glial cancer progenitor cells (GSCs) are developing into different grades of glioma: grade II diffuse astrocytoma, grade III anaplastic astrocytoma, and grade IV primary and secondary glioblastomas. In this research series of surgical specimens with different clinical cases have been analyzed by RT-qPCR. GBM is built by hierarchies developed by highly tumorigenic (GSCs) which are control by signaling mechanisms, including Notch, Wnt, BMP, TGFb and RTK pathways. Therefore we have studied the expression of some of these genes in progression of astrocytomas and GBM by RT-qPCR; in particular growth factor receptors EGFR, PDGFR, FGFR, Notch; members of corresponding signaling pathways, including cytoplasmic and nuclear intermediates (MELK, MAP, TUBB3, GFAP and CDK4, CDK6, MDM2,GAPDH, respectively); as well as transcription factors (OLIG2, SOX2, OCT4, NANOG). Some marker of SCs and neural differentiation had also been included, like CD133.

Conclusions:
The level of expression of egfr have been increased in the majority of the specimens of GBM compared to ones of diffuse and anaplastic astrocytomas.
The rate of expression of pdgfr was fairly similar; though pdgfr expression level was lower.
Both genes could be developed to diagnostic markers.

Expression level of transcription factors (sox2, oct4, nanog) involved in maintenance of stemness was increased in all samples. This observation exhibit possible relationship between stemness and GBM progression.

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