Molecular Markers And Molecular Typing Of Glioma Based On Pseudogenes

Part IA pseudogene-signature in glioma predicts survivalObjective Pseudogene was recognized as a potential tumor suppressor or oncogene in varies of diseases, however its roles in glioma have not been investigated. Our study was to identify the pseudogene-signature that predicted glioma survival.Methods Using a pseudogene-mining approach, we performed pseudogene expression profiling in 183 glioma samples from the Chinese Glioma Genome Atlas (CGGA) and set it as the training set. We found a six-pseudogene signature correlated with patients’ clinical outcome via bioinformatics analyses, and validated it in the Repository of Molecular Brain Neoplasia Data (REMBRANDT) containing 350 cases.Results We found a six-pseudogene signature correlated with patients’ clinical outcome via bioinformatics analyses (P< 0.01). A formula calculating the risk score based on the six-pseudogene signature was introduced and the patients of CGGA set were classified into high-risk group and low-risk group with remarkably different survival (P< 0.001) based on their scores. The prognostic value of the signature was confirmed in the REMBRANDT set.Conclusion The six-pseudogene biomarker is a valuable in predicting survival. Though the function of these pseudogenes is not clear, the identification of the prognostic pseudogenes indicated the potential roles of pseudogenes in glioma pathogenesis and they may have clinical implications in treating glioma.PARTⅡ Pseudogene ANXA2P2 indicates a poor prognosis and malignant progression in gliomaObjective Traditional diagnosis and treatment of glioma was not working well. Molecular diagnostics and targeted therapy depend on the discovery of biomarkers and biotargets. Pseudogene was found to be a potential oncogene or suppressor, which may play an important role in post-transcriptional regulation. We aimed to find a new pseudogene biomarker related with malignant progression and survival of glioma.Methods The REMBRANDT database was used as a experimental set and analyzed via a bioinformatics way. A pesudogene related with malignance and survival was identified. The GSE4290 database was used as a validation set.Results ANXA2P2 was found to be related with malignance and survival significantly (p<0.01). As the malignance progress, the expression of ANXA2P2 increased, and high expression group was related with shorter survival.Conclusion ANXA2P2 was significantly related with malignant progression and prognosis of glioma, whose function may be achieved by post-transcriptional regulation. It might be a worthy biomarker of both predictive and prognostic value.Part Ⅲ Pseudogene HLA-DRB6 in glioma indicate a poor prognosis and promote tumor progressionObjective Glioma was hard to be cured in traditional treatment. New molecular targeted therapy and immunity therapy depend on the discovery of new specific biomarkers. We aimed to find a pseudogene gene-marker which has predictive value in tumor progression and survival.Methods The CGGA database was used as an experimental set and analyzed via a bioinformatics way. A pesudogene related with malignance and survival was identified. The REMBRANDT database was used as a validation set.Results Pseudogene HLA-DRB6 was identified as a biomarker in predicting tumor progression and prognosis. As the tumor malignance progress, the expression of HLA-DRB6 increased. High expression group had a shorter survival time compared to low expression group. It can be validated in the REMBRANDT database.Conclusion Pseudogene HLA-DRB6 can be a worthy biomarker in predicting tumor progression and survival. It may play an important role in specific cellular immune response regulation.Part Ⅳ Molecular classification of primary glioblastoma based on pseudogene profilingObjective molecular subtypes based on objective genetic alterations may permit a more rational, patient-specific approach to molecular targeted therapy across various cancers. Molecular subtypes of primary glioblastoma (pGBM) were rare. The objective of this study was to subtype pGBM based on pseudogene profiling.Methods we analyzed pseudogene expression profiles from 85 pGBM samples. REMBRANDT dataset was used for validation.Results Two distinct subgroups of pGBM, based on a six-pseudogene marker, with different prognoses, were identified. The P2 subtype with more IDH1 mutations confers a poor prognosis. The P1 subtype with more MGMT promoter methylation status and higher EGFR expression confers a relatively better prognosis compared with the P2 subtype. We confirmed our found in REMBRANDT dataset.ConclusionGenome-wide pseudogene profiling of primary glioblastoma reveals two subtypes with different prognoses, which may optimize our impression of molecular classification. It would be more efficient for targeted and personal therapy combining with other classifications.