Whole-transcriptome sequencing profiling identifies functional and prognostic signatures in patients with PTPRZ1-MET fusion-negative secondary glioblastoma multiforme

Gliomas are the most common type of primary brain tumor in adults with a high mortality rate. Low-grade gliomas progress to glioblastoma multiforme (GBM) in the majority of cases, forming secondary GBM (sGBM), followed by rapid fatal clinical outcomes. Protein tyrosine phosphatase receptor type Z1 (PTPRZ1)-MET proto-oncogene receptor tyrosine kinase (MET) (ZM) fusion has been identified as a biomarker for sGBM that is involved in glioma progression, but the mechanism of gliomagenesis and pathology of ZM-negative sGBM has remained to be fully elucidated. A whole-transcriptome signature is thus required to improve the outcome prediction for patients with sGBM without ZM fusion. In the present study, whole-transcriptome sequencing on 42 sGBM samples with or without ZM fusion from the Chinese Glioma Genome Atlas database identified mRNAs with differential expression between patients with and without ZM fusion and the most significant survival-associated genes were identified. A 6-gene signature was identified as a novel prognostic model reflecting survival probability in patients with ZM-negative sGBM. Clinical characteristics in patients with a high or low risk score value were analyzed with the Kaplan-Meier method and a two-sided log-rank test. In addition, ZM-negative sGBM patients with a high risk score exhibited an increase in immune cells, NF-κB-induced pathway activation and a decrease in endothelial cells compared with those with a low risk score. The present study demonstrated the potential use of a next-generation sequencing-based cancer gene signature in patients with ZM-negative sGBM, indicating possible clinical therapeutic strategies for further treatment of such patients.