Dysregulation of PI3K/AKT signaling pathway in uterine leiomyoma: paired tissue-specific in-situ analysis.

BACKGROUND

Uterine leiomyoma is the most prevalent monoclonal benign tumor of the female reproductive tract, originating from the myometrium and frequently associated with significant gynecological morbidity. The PI3K/AKT signaling pathway plays a central role in regulating cellular proliferation, survival, and metabolic homeostasis, and its aberrant activation has been implicated in leiomyoma pathogenesis. The present study investigated the tissue-specific expression profile of key PI3K/AKT pathway genes in a large paired tissue cohort comprising leiomyoma and adjacent myometrium samples.

METHODS

Reverse transcription-quantitative real-time PCR (RT-qPCR) was performed to evaluate the mRNA expression of PI3K, AKT3, MTOR, PDK1, and PTEN in paired leiomyoma and adjacent myometrium tissues obtained from the same uterus. A total of 171 paired tissue samples were included in the analysis. GAPDH was used as a housekeeping gene for normalization. The ΔΔCt method was used to calculate relative gene expression levels. Statistical significance was defined as p < 0.05. Integrated bioinformatic analyses were additionally performed to assess pathway-level interactions and functional associations.

RESULTS

RT-qPCR analysis revealed significant upregulation of PI3K, AKT3, and MTOR expression in leiomyoma tissues, whereas PTEN expression was significantly reduced in comparison with matched myometrium tissues (p < 0.05). These findings indicate coordinated dysregulation of the PI3K/AKT signaling axis, which may contribute to leiomyoma growth and survival. Bioinformatic analyses further supported the functional interconnectivity and enrichment of the studied pathway components.

CONCLUSIONS

The present findings support the involvement of PI3K/AKT signaling dysregulation in uterine leiomyoma pathogenesis. The coordinated upregulation of proliferative signaling components alongside reduced PTEN expression suggests altered signaling regulation within leiomyoma tissue. Further validation in larger cohorts, along with protein-level and functional studies, is required to better define the biological and clinical significance of these findings.