Signal Transducer and Activator of Transcription 4 (STAT4) as a Predictor of Pituitary Adenoma Recurrence

Introduction Pituitary adenomas (PAs) are benign tumors of the pituitary gland, a small structure at the brain’s base responsible for hormone regulation [1]. Although typically slow-growing and non-metastatic, PAs can cause complications if they enlarge and press on surrounding brain structures [2]. Growing evidence suggests that genetic factors contribute to PA development, with Signal Transducer and Activator of Transcription 4 (STAT4) emerging as a key focus. STAT4 regulates gene expression and modulates immune responses [3], and its dysregulation or overactivation may promote inflammation, potentially influencing oncogenesis. This study explores STAT4’s role in PA pathogenesis, uncovering potential links that could inform future therapies and deepen our understanding of the disease. Aim This study aims to investigate whether STAT4 contributes to PA recurrence by examining STAT4 polymorphisms and serum levels. Methods Examining 139 patients with PA and 357 healthy subjects, DNA samples from peripheral blood leukocytes were purified using the DNA salting-out method. Real-time polymerase chain reaction (RT-PCR) assessed STAT4 (rs7574865, rs10181656, rs7601754, and rs10168266) single nucleotide polymorphism (SNPs), and enzyme-linked immunosorbent assay (ELISA) determined the levels of STAT4 in blood serum. The analysis was conducted using “IBM SPSS Statistics 29.0“. Results For PA recurrence, the rs7574865 G allele was less frequent in PA without recurrence (p = 0.012), and the GT+GG genotypes were associated with a 1.8-fold increase in PA without recurrence (p = 0.008). Serum STAT4 levels were higher in PA patients compared to the reference group (p < 0.001). Elevated STAT4 serum levels were observed in PA patients with the STAT4 rs10181656 CC or CG genotypes (CC: p = 0.004; CG: p = 0.023) and with the rs7574865 GG or GT genotypes (GG: p = 0.003; GT: p = 0.021). PA patients with the STAT4 rs7601754 AA genotype exhibited higher serum levels compared to the reference group (p < 0.001). Similarly, higher serum levels were found in PA patients with STAT4 rs10168266 CC or CT genotypes (CC: p = 0.004; CT: p = 0.027). Conclusions STAT4 genetic variations and serum levels are linked to PA recurrence. The rs7574865 G allele was less frequent in non-recurrent PA, suggesting a protective effect. Also, PA patients had higher STAT4 levels. These findings highlight STAT4’s potential as a biomarker for PA recurrence and targeted therapy. Further research is needed to explore its potential as a target for personalized treatment strategies.