The Prognostic Role of STAT5B Across Cancer Types and Comparative Analysis with STAT5A: A Systematic Review

The signal transducer and activator of transcription 5 (STAT5) proteins, STAT5A and STAT5B, are highly homologous transcription factors with distinct roles in cancer biology. While STAT5A has been characterized as a context-dependent modulator of tumor progression, the prognostic significance of STAT5B remains less clear. Here, we conducted a systematic meta-analysis of STAT5B to evaluate its association with overall survival across cancers and to compare its prognostic role with that of STAT5A, as reported previously.

Microarray datasets from the Prognoscan database were analyzed for STAT5B expression and overall survival. Hazard ratios (HRs) were estimated using Cox proportional hazards models, and results from 42 datasets were synthesized by meta-analysis. Subgroup analyses were performed by cancer type, and heterogeneity was assessed using Cochran's Q Test and I² statistics.

Pooled analysis showed that high STAT5B expression was significantly associated with favorable overall survival (lnHR = -0.4009; 95% CI: -0.6007 to -0.2011; p < 0.0001), albeit with notable heterogeneity (I² = 64%). Subgroup analyses indicated that STAT5B was particularly protective in lung cancers (lnHR = -0.5170; p = 0.0042) and hematologic malignancies (lnHR = -0.6988; p < 0.0001). In contrast, STAT5A demonstrated divergent effects, conferring favorable survival in breast cancer but poorer outcomes in hematologic cancers.

Elevated STAT5B expression is associated with improved survival in multiple cancers, supporting a potential tumor-suppressive role distinct from STAT5A. These findings underscore the importance of isoform-specific STAT5 evaluation in cancer prognosis and suggest that STAT5B may serve as a potential biomarker and therapeutic target.