The role of p-Stat3 Y705 immunohistochemistry in glioblastoma prognosis

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.

The Implications of Noncoding RNAs in the Evolution and Progression of Nonalcoholic Fatty Liver Disease (NAFLD)-Related HCC

“…In addition, the research group reported an association between the ectopic expression of miR-155 and the growth of HCC cells, while its downregulation inhibited their growth [ 182 ]. The oncogenic behavior of hepatic miR-155 was also confirmed by Yan et al They correlated its elevation with the downregulation of SOCS1, which activated STAT3, previously confirmed as an important prognostic biomarker in other cancers, such as glioblastoma [ 183 ], and further downregulated MMP9 expression, consequently promoting HCC tumor invasiveness [ 184 ]. Research on animal models shows that hepatic miR-155 overexpression has a protective role in NAFLD and, paradoxically, a tumor-promoting one in HCC [ 185 ].…”

Loss of cell–cell adhesion triggers cell migration through Rac1-dependent ROS generation

“…The role of STAT3 in tumor formation and progression has been extensively studied in many human cancers ( Kusaba et al, 2005 ; Diaz et al, 2006 ; Banerjee et al, 2016 ; Li et al, 2019 ; Susman et al, 2019 ; Marginean et al, 2021 ), including HNSCC ( Mali, 2015 ; Geiger et al, 2016 ). Aberrant activation of STAT3 leads to the increased expression of downstream target genes, leading to increased cell proliferation, cell survival, angiogenesis, and immune system evasion ( Yu et al, 2014 ).…”

Wild‑type KRAS inhibits the migration and invasion of pancreatic cancer through the Wnt/β‑catenin pathway

“…Studies have shown that STAT3/p-STAT3 is highly expressed in a variety of tumors and its activation product, p-STAT3, is associated with tumor grade and patient prognosis ( 33 , 34 ). As a major mediator of the JAK/STAT pathway, STAT3 may be an important regulator of tumor progression by enhancing aggressiveness or promoting EMT ( 35 , 36 ).…”