Sox11 expression in astrocytic gliomas: correlation with nestin/c-Met/IDH1-R132H expression phenotypes, p-Stat-3 and survival

Abstract

Background:Sox11 is a transcription factor expressed in foetal and neoplastic brain tissue, including gliomas. It has been shown to suppress the tumourigenicity of glioma stem cells in vivo, thereby being hypothesised to function as a tumour suppressor.Methods:We investigated the expression of Sox11 in 132 diffuse astrocytomas in relation to the regulator cell marker nestin, c-Met and IDH1-R132H, which have shown to be differentially expressed among the molecular subgroups of malignant gliomas, as well as to an inducer of astrocytic differentiation, that is, signal transducer and activator of transcription (p-STAT-3), clinicopathological features and survival.Results:Sox11 immunoreactivity was identified in all tumours irrespective of grade, but being correlated with p-STAT-3. Three out of seven cases showed partial Sox11 promoter methylation. In >50% of our cases neoplastic cells coexpressed Sox11 and nestin, a finding further confirmed in primary glioblastoma cell cultures. Furthermore, nestin, c-Met and IDH1-R132H expression differed among grade categories. Cluster analysis identified four groups of patients according to c-Met, nestin and IDH1-R132H expression. The c-Met/nestin high-expressor group displayed a higher Sox11 expression. Sox11 expression was an indicator of favourable prognosis in glioblastomas, which remained in multivariate analysis and validated in an independent set of 72 cases. The c-Met/nestin high-expressor group was marginally with shorter survival in univariate analysis.Conclusions:We highlight the importance of Sox11 expression as a favourable prognosticator in glioblastomas. c-Met/nestin/IDH1-R132H expression phenotypes recapitulate the molecular subgroups of malignant glioma.

SOX11 regulates apoptosis and cell cycle in hepatocellular carcinoma via Wnt/β‐catenin signaling pathway

“…HCC is one of the most common and aggressive malignancies worldwide and is often accompanied by a high recurrence rate and poor prognosis after surgery, which are mainly attributed to the proliferative, invasive, and migratory capabilities of HCC cells . SOX11 is recognized as a type of transcription factor that belongs to the HMG box protein superfamily . The function of SOX11 is mainly associated with neural development and organogenesis during embryonic development .…”

Immunocytochemistry for SOX‐11 and TFE3 as diagnostic markers for solid pseudopapillary neoplasms of the pancreas in FNA biopsies

“…SOX‐11 is known to be expressed in hematopoietic and glial malignancies such as mantle cell lymphoma and astrocytic gliomas; however, its role in solid tumors such as SPNs is still unknown. In a recent publication, Li et al reported that according to a microarray analysis, SOX‐11 was found to be exclusively expressed in SPNs in comparison with normal pancreas, pancreatic adenocarcinomas, and pancreatic NETs .…”

“…SOX‐11 is localized on chromosome 2p25.3 and has been shown to be critical in embryonic neurogenesis and neuronal cell fate . SOX‐11 gene mutations have also been previously associated with malignancies such as mantle cell lymphoma and gliomas . More recently, SOX‐11 messenger RNA has shown to be consistently increased in SPNs by RNA microarray analysis …”

“…7,8 SOX-11 gene mutations have also been previously associated with malignancies such as mantle cell lymphoma and gliomas. 9,10 More recently, SOX-11 messenger RNA has shown to be consistently increased in SPNs by RNA microarray analysis. 11 TFE3 is a member of the microphthalmia family of transcription factors (ie, the MiT family), which are considered oncogenes.…”

Molecular prognostic factors in glioblastoma: state of the art and future challenges

“…Several studies have tried to correlate the expression of these markers with GBM patient prognosis, but no consistent associations have currently been established [136]. For example, some studies report an association between CD133, Nestin, cJun, CD44 and ID1 expression and GBM patient poor prognosis [10, [119][120][121]135,137], while others suggest an association of CD133 and SOX-11 expression with longer prognosis [24,122]; other studies report no effects on GBM patient survival due to the expression of Nestin, CD133 and CD15 [138,139]. The contradictory findings regarding the clinical relevance of these putative stem cell markers in GBM warrants further investigation.…”