Abstract 1503: HP1-gamma's expression correlates with glioma grade and survival and is a putative marker of glioma stem like cells

Abstract

Genetic and signaling pathways involved in the development of glioblastoma have been relatively well characterized. Gene/protein expression profiles of glioblastoma have been described that reflect stem-like phenotype of the tumor. However, no reliable individual markers exist up-to-date that differentiate glioblastoma stem-like cells from the neural stem cells. Glioblastoma appears to be of heterogenous cellular population, but detailed cellular origin of these tumors is unknown. Using a label-free proteomic approach, we analyzed two different glioma models with proven de novo tumorigenic properties, and compared them with primary neurospheres. Of almost 2000 identified proteins, we found 482 to be significantly differentially expressed among the three groups. Among the identified substrates, the clusters of proteins with highest density of protein-protein interactions were functionally enriched in RNA processing related to development and metabolic processes. We then focused on two putative quantitative markers of glioma stem-like cells, HP1-gamma (Heterochromatin Protein 1- gamma) - CBX3 (chrome box 3), an epigenetic regulator involved in RNA processing, and LDHA (Lactate Dehydrogenase A), a key metabolic enzyme of anaerobic glycolysis. We quantitated their expression in glioma tissue of different grades in a large set of patient samples and were able to show that the expression of HP1-gamma, highly upregulated in glioblastoma stem-like cells, correlates to glioma grade. Independent analysis of publicly available glioma patient data showed that LDHA expression is linked to IDH1 mutation status both in high grade and low grade gliomas. The same analysis reinforced our findings towards an increased involvement of CBX3/HP1-gamma in high grade gliomas. Altogether, CBX3/HP1-gamma and LDHA are novel biomarkers for cancer stem cell phenotype with different clinical importance in gliomas. Citation Format: Uros Rajcevic, Sabrina Fritah, Petr V. Nazarov, Mara Popovic, Rajko Kavalar, Tadej Strojnik, Neza Podergajs, Jaco C. Knol, Thang V. Pham, Sander R. Piersma, Connie R. Jimenez, Simone P. Niclou. HP1-gamma's expression correlates with glioma grade and survival and is a putative marker of glioma stem like cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1503. doi:10.1158/1538-7445.AM2015-1503