Abstract
The signal transducers and activators of transcription genes family (STATs) have been well studied as prognostic predictors for various solid tumors, but their prognostic values in gastric cancer (GC) patients have not been fully elucidated. The ‘Kaplan–Meier plotter’ and multiple public available databases were used for the characterization of the prognostic roles of STATs family in GC. The results indicated that high mRNA expression of all individual STATs, except STAT3 and STAT6, were significantly associated with favorable overall survival (OS) in GC. Moreover, the prognostic values of STATs were further characterized in subtypes, including HER2 status, Lauren’s classification, differentiation, and clinical stages. Moreover, the prognostic value of STATs signature was also characterized. Low risk group displayed a significantly favorable OS than high risk (HR: 1.71; 95% CI: 1.09–2.66, P=0.0184). In addition, STATs showed distinct expression between GC and normal groups. Meanwhile, comparable high correlation between STATs and tumor immune infiltrating cells (TIICs) was also observed. STAT4 displayed highest correlation with dendritic cells (correlation = 0.716, P=1.63e-59) and CD8+ T cells (correlation = 0.697, P=5.02e-55). In conclusion, our results suggest that all individual STATs, except STAT3 and STAT6, may act as prognostic markers in GC.
Highlights
Gastric cancer (GC) is the fourth most common cancer and second leading cause of cancer-related deaths in the world, accounting for approximate 9% of total cancer deaths [1,2]
High mRNA expression of STAT1 (HR: 0.71; 95% confidence intervals (CI): 0.57–0.89; P=0.0025), STAT2 (HR: 0.75; 95% CI: 0.57–1; P=0.05), STAT4 (HR: 0.76; 95% CI: 0.61–0.94; P=0.013), STAT5a (HR: 0.81; 95% CI: 0.66–1; P=0.05), and STAT5b (HR: 0.81; 95% CI: 0.67–0.98; P=0.029) were associated with better overall survival (OS) (Figure 1B–F)
STAT6 (HR: 0.82; 95% CI: 0.66–1.02; =0.076) and STAT3 (HR: 1.21; 95% CI: 0.89–1.65; P=0.23) did not show significant prognostic values (Figure 1A)
Summary
Gastric cancer (GC) is the fourth most common cancer and second leading cause of cancer-related deaths in the world, accounting for approximate 9% of total cancer deaths [1,2]. Signal transducers and activators of transcription (STATs) are a gene family of cytoplasmic transcription factors, consisting of seven members, STAT1–STAT4, STAT5a, STAT5b, and STAT6 [5,6]. STATs play important roles in numerous biological processes, including cell proliferation, differentiation, apoptosis, and survival [7]. STATs are activated via tyrosine phosphorylation, a process which occurs either through KIT-based interaction or cytokine-induced JAK pathway [8]. STATs can be activated by constitutively activated non-receptor protein tyrosine kinases (PTKs), including c-Src and Bcr-Abl. Activated STATs rapidly translocate into nucleus, and bind to the promoter region of target genes, serving as transcription regulators. The prognostic values of STATs family in GC patients are yet to be fully characterized
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