Epigenetic Downregulation of PTEN in Gallbladder Cancer.

Abstract

Gallbladder cancer (GBC) is becoming a global health problem. Phosphatase and tensin homolog (PTEN), also known as guardian gene of cancer, encodes a protein, which dephosphorylates phosphatidylinositol (3,4,5) triphosphate {PtdIns (3,4,5) P3 } into phosphatidylinositol (4,5) diphosphate {PtdIns (4,5) P2} that results in the inhibition of AKT/PKB signaling pathway. PTEN plays a key role in the pathogenesis of various cancers. However, its role in GBC is still obscure. The present study was aimed to identify the epigenetic role of PTEN in GBC and GSD. PTEN promoter methylation was studied by methylation-specific PCR in 50 GBC and 30 GSD tissues. Transcript level expression of PTEN was analyzed by reverse transcriptase PCR and quantitative PCR in 20 GBC and 20 GSD tissue samples. Immunohistochemistry was performed on tissue microarrays of 136 GBC samples to correlate the methylation pattern with the pattern of in situ expression of PTEN protein. Student's t test was performed to test the significant level of difference between case and control samples. Values showing p≤0.05 were considered significant. MS PCR showed PTEN promoter methylation in 30% (15/50) GBC (p=0.0486) and 22.86% (8/30) GSD (p=0.0530) cases. RT-PCR and qPCR revealed downregulation of PTEN in advanced GBC cases (p<0.0001), but, not in GSD (p=0.901). Immunohistochemistry of GBC tissue microarray scored 1+ in 20.29% (p=0.0028) and zero or negative in 50% (p<0.0001) GBC cores. Thus, PTEN may be considered asa useful biomarker for the management of GBC, however, needs larger sample size to validate it further.