The Research Of GBM Intratumoral Heterogeneity And Micro-Environment Heterogeneity Based On Single Cell Transcriptome Sequencing

Glioblastoma(GBM)is the most common and aggressive malignant brain tumor in adults.The current treatment which includes surgical resection,radiation,and chemotherapy generally results in a poor prognosis.Increasing evidence indicated that the high heterogeneity and vascular density in GBM were crucial factors for accelerating the lethal recurrence.To promote the precision medicine,a large number of molecular signature-based subtyping methods have been proposed in the last decades,which leverages a profound impact on the clinical treatment.By integrating huge amounts of high-throughput data,the latest study has divided the GBM samples into three subtypes,including proneural(PN),classical(CL),and mesenchymal(MS)Recent researches revealed that the GBM subtypes were strongly associated with tumor microenvironment(TME),indicating that the heterogeneity of GBM and TME may play a pivotal role on treatment resistance and relapse.However,the current subtyping tools were mainly developed based on the tumor bulk data,which can only extract a part of common features in the focus and limit the ability for identify the specific tumor cells,such as tumor stem cells.Here,we explored the GBM heterogeneity in a single-cell level,and found five groups of GBM cells,including NR(Neuron-like),NM(Neuron/Normal),MT(Mitochondrial-associated),MTA(Mitochondrial and angiogenesis-associated),and STC(Stem cell-like).There exhibited a variety of biological functions and clinical features among the groups.For instance,the NR and NM were both associated with low degree of malignancy,of which the molecular signatures were quite similar to that of neuron cells;Both of the MT and MTA underwent an abnormal energy metabolism,but the angiogenesis pathway was significantly activated in the MTA rather than the MT.The tumor cells in MT and MTA group were strongly associated with classical and mesenchymal subtype respectively;The STC was more likely to possess the stem cell ability and exhibited a high degree of malignancy.The survival analysis showed that the increasing enrichment of STC was significantly associated with the decline of survival time.Besides,we found there was a positive correlation between the MTA and STC.By contrast,the NR and NM seemed to exhibit a competition relationship across all of tumor regions.We also found there was a relationship between STC and mast cells(MCs).The patients with both STCs and MCs accumulation implied a poor prognosis.Taken together,these findings may give a bran-new sight into the interaction between GBM cells and microenvironment,and provide theoretical basis for the cancer cell biological functional research and the clinical trials.