Diagnostic Utility of the Immunohistochemical Expression of Serine and Arginine Rich Splicing Factor 1 (SRSF1) in the Differential Diagnosis of Adult Gliomas

Abstract

Background: The aim of this study was to investigate the immunohistochemical expression and distribution of serine and arginine rich splicing factor 1 (SRSF1) in a series of 102 cases of both diffuse and circumscribed adult gliomas to establish the potential diagnostic role of this protein in the differential diagnosis of brain tumors. Methods: This retrospective immunohistochemical study included 42 glioblastoma cases, 21 oligodendrogliomas, 15 ependymomas, 15 pilocytic astrocytomas, 5 sub-ependymal giant cell astrocytoma and 4 pleomorphic xanthoastrocytomas. Results: Most glioblastoma (81%), oligodendroglioma (71%), sub-ependymal giant cell astrocytoma (80%) and pleomorphic xanthoastrocytoma (75%) cases showed strong SRSF1 immunoexpression, while no detectable staining was found in the majority of ependymomas (87% of cases) and pilocytic astrocytomas (67% of cases). Conclusions: The immunohistochemical expression of SRSF1 may be a promising diagnostic marker of astrocytomas and oligodendrogliomas and its increased expression might allow for excluding entities that often enter into differential diagnosis, such as ependymomas and pilocytic astrocytomas.

Nuclear Respiratory Factor-1, a Novel SMAD4 Binding Protein, Represses TGF-β/SMAD4 Signaling by Functioning as a Transcriptional Cofactor

“…To understand the NRF1 and SMAD4 protein-protein interaction more completely, an extensive analysis of each protein and/or structural biology studies will be required. Recently, Barbagallo, D et al and Broggi, G et al reported that the RNA-binding motif responsible for the interaction between Serine and Arginine Rich Splicing Factor 1 (SRSF1) and circSMARCCA5 (a 269-nucleotide-long circRNA) are coupled with increased amounts of total Vascular Endothelial Growth Factor A (VEGFA) mRNA secretion and the recommended use of SRSF1 as a diagnostic immunomarker in gliomas [34,35]. In the case of NRF1, it appears to be both a negative regulator and an interaction partner of SMAD4.…”

Immunohistochemical Expression of Serine and Arginine-Rich Splicing Factor 1 (SRSF1) in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Study

“…In addition, some authors [ 29 , 31 , 32 , 33 ] previously demonstrated on human glioblastoma tissue samples that SRSF1 also acted as a pro-angiogenic factor, being part of a molecular axis, mediated by circSMARCA5—a circular RNA that regulated cell migration and angiogenesis through the binding of SRSF1—and involved in the splicing of the Vascular Endothelial Growth Factor A. (VEGF-A).…”

“…(VEGF-A). The splicing process of VEGF-A pre-mRNA may alternatively generate both a pro-angiogenic and an anti-angiogenic isoform [ 29 , 31 , 32 ]; the above-mentioned authors [ 29 , 31 , 32 , 33 ] hypothesized that the upregulation of SRSF1 led to an angiogenic stimulation on GBM tissue, through the switch of the proangiogenic/antiangiogenic ratio of VEGF-A.…”

Serum Extracellular Vesicle-Derived circHIPK3 and circSMARCA5 Are Two Novel Diagnostic Biomarkers for Glioblastoma Multiforme

“…We recently characterized circSMARCA5 as a tumor-suppressive circRNA, downregulated in GBM tissue when compared to normal brain parenchyma; its expression is inversely correlated with: (i) overall and progression-free survival of GBM patients; (ii) pro- to anti-angiogenic VEGFA mRNA isoform ratio; and (iii) microvascular density of GBM tissue [ 31 ]. Mechanistically, we determined that circSMARCA5 physically interacts with the oncoprotein SRSF1 through its GAUGAA RNA motif: mutation of this motif determined a significant decrease in the binding between the two molecules with related downstream effects on GBM cell migration and angiogenic potential [ 32 , 44 ]. To further characterize the molecular phenotype of GBM patients, we assayed the expression of circSMARCA5 and other circRNAs known to be dysregulated in GBM in EVs isolated from serum (sEVs) of GBM patients and compared these data to those from unaffected controls (UC).…”