Abstract
BackgroundIn spite of the multimodal treatment used today, glioblastoma is still the most aggressive and lethal cerebral tumour. To increase survival in these patients, novel therapeutic targets must be discovered. Signal transducer and activator of transcription 3 (Stat3), a transcription factor that controls normal cell differentiation and survival is also involved in neoplastic celltransformation. In this study we evaluated the immunohistochemical expression of pY705-Stat3 in patients with primary glioblastoma and determined its prognostic role by correlating it with survival.MethodsThis retrospective study included 94 patients diagnosed with glioblastoma. We determined the localization, number of positive cells, and marker intensity for pY705-Stat3 in these patients with the use of immunohistochemistry. The prognostic role was determined by correlating pY705-Stat3 expression on formalin-fixed paraffin-embedded tumour tissues with the patient’s survival in univariate and multivariate COX regressions.ResultsWe found a statistically significant difference in survival between the patients with more than 20% pY705-Stat3 positive cells and those with less than 20% pY705-Stat3 positive cells (8.9 months median survival versus 13.7 months medial survival, p < 0.001). On multivariate analyses with the COX proportional hazards regression model including pY705-Stat3 expression, age and relapse status, pY705-Stat3 status was an independent prognostic factor in glioblastoma (P < 0.001).ConclusionThe results obtained show that the immunohistochemical expression of pY705-Stat3 correlates with survival in glioblastoma. This study identifies Stat3 as a possible target for existing or new developed Stat3 inhibitors.
Highlights
In spite of the multimodal treatment used today, glioblastoma is still the most aggressive and lethal cerebral tumour
Susman et al Diagnostic Pathology (2019) 14:124 adaptation in glioblastoma have shown that the major signalling pathways activated in hypoxia are those of the hypoxic inducible factor 1α (HIF-1α) vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFβ), mammalian target of rapamycin, CD133, as well as of signal transducer and activator of transcription 3 (Stat3) [6,7,8,9]
The multivariate model includes all the variables in the table A second model was created adding to these variables, gender, as well as tumour volume, where we found hazards regression (HR) p-Signal transducer and activator of transcription 3 (Stat3) percentage ≥ 20% = 4.86, p < 0.001 HR Hazard ratio, CI Confidence interval
Summary
In spite of the multimodal treatment used today, glioblastoma is still the most aggressive and lethal cerebral tumour. Signal transducer and activator of transcription 3 (Stat3), a transcription factor that controls normal cell differentiation and survival is involved in neoplastic celltransformation. Adaptation to hypoxia leads to the specific activation of the genetic programs and signalling pathways that are involved in the stem-like phenotype or epithelialmesenchymal (EMT) transition, with the subsequent increase in resistance to chemotherapy and radiotherapy [4,5,6]. Susman et al Diagnostic Pathology (2019) 14:124 adaptation in glioblastoma have shown that the major signalling pathways activated in hypoxia are those of the hypoxic inducible factor 1α (HIF-1α) vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFβ), mammalian target of rapamycin (mTOR), CD133, as well as of signal transducer and activator of transcription 3 (Stat3) [6,7,8,9]. Stat is activated by phosphorylation; after dimerization it translocates into the nucleus, where it binds to the DNA, activating specific cellular pathways [12]
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