PI3K/AKT pathway genetic alterations and dysregulation of expression in bladder cancer

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• The Phosphoinositide 3-kinase (PI3K)/AKT signaling pathway plays a critical role in cellular processes, including proliferation, survival, and metabolism.
• Dysregulation of the PI3K/AKT pathway is frequently observed in various cancers, including urinary bladder cancer.

Purpose of the Study:

• To investigate the specific roles of PI3K/AKT pathway components in the development and progression of urinary bladder cancer.
• To identify potential biomarkers for prognosis and therapeutic selection in bladder cancer management.

Main Methods:

• Genomic DNA and total RNA were isolated from 65 bladder tumors and 13 normal bladder tissues.
• Sanger sequencing was performed on laser-microdissected tissues to identify PIK3CA mutations.
• RT-PCR and immunohistochemistry were used to analyze PTEN and p-AKT expression levels.

Main Results:

• Three pathogenic mutations in PIK3CA exon 20 were identified.
• PTEN mRNA expression was downregulated in bladder cancer tissues compared to normal tissues.
• p-AKT expression varied with tumor grade and stage, showing upregulation in low-grade tumors and downregulation in infiltrating carcinomas.
• PTEN expression patterns differed between superficial and infiltrating tumors, with nuclear localization correlating with infiltrating carcinomas.

Conclusions:

• Activation of the PI3K/AKT pathway is essential for bladder cancer initiation and progression.
• PIK3CA mutations, p-AKT, and nuclear PTEN expression are potential biomarkers for predicting prognosis and guiding therapy selection in bladder cancer patients.