Identification of STAT5B as a biomarker for an early diagnosis of endometrial carcinoma

Abstract

Background: The late detection of endometrial carcinoma (EC) at an advanced stage often results in a poor patient prognosis. It is hence important to identify reliable biomarkers to facilitate early detection of EC. Signal transducer and activator of transcription (STAT) family members play an important role in several tumors, however, their impact on EC development and progression remains unclear. Methods: Machine learning methods were used to investigate the importance of STAT5B in EC. Results: Hence, we explored the UALCAN data mining platform and found that while STAT1 and STAT2 were upregulated, STAT5A, STAT5B, and STAT6 were downregulated in EC.This high expression of STAT5B and STAT6 predicted favorable clinical outcomes, whereas the increased expression of STAT1 and STAT2 predicted poor clinical outcomes. Subsequent pathway enrichment analysis revealed that the STAT family was mainly involved in apoptosis pathway activation, cell cycle disruption, and epithelial-mesenchymal transition. Drug sensitivity analysis demonstrated that STAT5A/5B expression was negatively correlated with drug resistance in EC. Further, the expression of STAT5B mRNA and protein was correlated with several clinicopathological characteristics. Tumor Immune Estimation Resource (TIMER) analysis revealed that STAT5B expression was positively correlated with the abundance of infiltrating CD8+ T cells and neutrophils while its copy number variation was associated with the overall immune cell infiltration. The data on the correlations between STAT5B expression and related genes in uterine corpus endometrial carcinoma (UCEC) in cBio Cancer Portal showed the closest correlation of STAT5B expression with that of KIAA0753 (also known as moonraker and OFIP), followed by COL27A1 in EC. Pathway enrichment analysis further showed that STAT5B-related genes were involved in the mitogen-activated protein kinase (MAPK) and Ras signaling pathways. Conclusion: Collectively, our findings provided new insights into the role of the STAT family in EC. It also highlighted new targets for future research on diagnostic and prognostic markers and STAT5B as a novel marker for drug sensitivity screening.