Abstract
Signal transducer and activator of transcription (STAT) family genes—of which there are seven members: STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, and STAT6—have been associated with the progression of multiple cancers. However, their prognostic values in glioma remain unclear. In this study, we systematically investigated the expression, the prognostic value, and the potential mechanism of the STAT family genes in glioma. The expression of STAT1/2/3/5A/6 members were significantly higher and positively correlated with IDH mutations, while the expression of STAT5B was lower and negatively correlated with IDH mutations in glioma. Survival analysis indicated that the upregulation of STAT1/2/3/5A/6 and downregulation of STAT5B expression was associated with poorer overall survival in glioma. Joint effects analysis of STAT1/2/3/5A/5B/6 expression suggested that the prognostic value of the group was more significant than that of each individual gene. Thus, we constructed a risk score model to predict the prognosis of glioma. The receiver operating characteristic curve and calibration curves showed good performance as prognostic indicators in both TCGA (The Cancer Genome Atlas) and the CGGA (Chinese Glioma Genome Atlas) databases. Furthermore, we analyzed the correlation between STAT expression with immune infiltration in glioma. The Protein–protein interaction network and enrichment analysis showed that STAT members and co-expressed genes mainly participated in signal transduction activity, Hepatitis B, the Jak-STAT signaling pathway, transcription factor activity, sequence-specific DNA binding, and the cytokine-mediated signaling pathway in glioma. In summary, our study analyzed the expression, prognostic values, and biological roles of the STAT gene family members in glioma, based on which we developed a new risk score model to predict the prognosis of glioma more precisely.
Highlights
Glioma is one of the most common cancers and leading causes of cancer-related deaths worldwide (Gagliardi et al, 2014; Zhang and Zhang, 2015)
STAT1, STAT3, STAT5A, STAT5B, and STAT6 mRNA expression levels were significantly upregulated in glioma
The results showed that the expression of STAT1, STAT2, STAT3, STAT5A, and STAT6 increased with increasing tumor grades
Summary
Glioma is one of the most common cancers and leading causes of cancer-related deaths worldwide (Gagliardi et al, 2014; Zhang and Zhang, 2015). The coiled-coil domain contributes to nuclear localization; the DBD domain is relevant to target gene transcription; the SH2 domain mediates homo- or heterodimerization of STATs; and the TAD domain is crucial for the activity of the STAT protein (Miklossy et al, 2013; Dorritie et al, 2014). An increasing number of studies have demonstrated that constitutive activation of STATs participates in the pathology of glioma. Activated STAT3 in glioma is associated with oncogenesis and cancer progression (de la Iglesia et al, 2009; Chai et al, 2016). Recent studies have shown that STAT3 may play a tumor suppressive function in glioma pathogenesis when associated with different levels of expression of PTEN (de la Iglesia et al, 2008)
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