SETMAR Shorter Isoform: A New Prognostic Factor in Glioblastoma

Abstract

Recent evidence suggests that the chimeric protein SETMAR is a factor of interest in cancer, especially in glioblastoma. However, little is known about the expression of this protein in glioblastoma tissues, and no study has been done to assess if SETMAR could be a prognostic and/or diagnostic marker of glioblastoma. We analyzed protein extracts of 47 glioblastoma samples coming from a local and a national cohort of patients. From the local cohort, we obtained localized biopsies from the central necrosis area, the tumor, and the perilesional brain. From the French Glioblastoma Biobank (FGB), we obtained three types of samples: from the same tumors before and after treatment, from long survivors, and from very short survivors. We studied the correlations between SETMAR amounts, clinical profiles of patients and other associated proteins (PTN, snRNP70 and OLIG2). In glioblastoma tissues, the shorter isoform of SETMAR (S-SETMAR) was predominant over the full-length isoform (FL-SETMAR), and the expression of both SETMAR variants was higher in the tumor compared to the perilesional tissues. Data from the FGB showed that SETMAR amounts were not different between the initial tumors and tumor relapses after treatment. These data also showed a trend toward higher amounts of S-SETMAR in long survivors. In localized biopsies, we found a positive correlation between good prognosis and large amounts of S-SETMAR in the perilesional area. This is the main result presented here: survival in Glioblastoma is correlated with amounts of S-SETMAR in perilesional brain, which should be considered as a new relevant prognosis marker.