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A Comprehensive Analysis of the Expression and Prognosis of STATs in Human Breast Invasive Carcinoma

Qin Huo, Ni Xie

Background: Multiple cancer types are associated with the Signal Transducer and Activator of Transcription (STAT) family of proteins. The expression and prognostic value of STATs in Breast Invasive Carcinoma (BRCA) remain unclear. Methods: Herein we investigated the clinical data onto 1,222 patients with BRCA based on the Cancer Genome Atlas (TCGA) database, UALCAN, cBio Cancer Genomics Portal (cBioPortal), STRING, and GeneMANIA databases.

Results: The transcriptional levels of STAT4/5A/5B/6 were significantly decreased while the transcriptional levels of STAT1 were elevated in BRCA tissues. A significant correlation exists between STATs expressions and known prognostic factors, e.g., age, pathologic stage, radiation therapy, and Tumor Node Metastasis (TNM) stages. It was discovered that patients with high STAT4 expression had a better prognosis for overall survival (OS) (HR=0.59, p=0.002), Disease-Specific Survival (DSS) (HR=0.59, p=0.018), and Progress Free Interval (PFI) (HR=0.55, p<0.001). STAT4 may be an independent prognostic marker for BRCA through univariate and multivariate Cox regression. In terms of immune infiltrating levels, a correlation between STAT1/2/4/13 expression and immune cell infiltration, including T cells and Th1, has also been noted. Furthermore, the levels of STAT4 were statistically significant correlated with T cells (r=0.822, p<0.001), cytotoxic cells (r=0.746, p<0.001), B cells (r=0.691, p<0.001), Th1 cells (r=0.686, p<0.001), and activated Dendritic Cells (DC).

Conclusion: Based on the findings of this study, STAT4 might serve as a novel prognostic biomarker to predict prognosis and levels of immune infiltration for BRCA.