Dysregulation of gene expression of PTEN and AKT signaling pathway in patients of ovarian cancer: A pilot study

Abstract

Objective: PI3K/AKT/mTOR signaling pathway has a crucial role in chemo- and radiotherapy resistance, and tumorigenesis of ovarian cancer. Some of the genes of this pathway are also linked with progression of disease in association of different miRNAs. The main objective of the current research was to determine the level of mRNA expression of different genes along with their respective microRNA (miRNAs) in ovarian cancer and apparently healthy women. Methods: Samples from 46 ovarian cancer and 46 healthy females were obtained from a local cancer hospital. mRNA and miRNAs were extracted and gene expression of mRNA and miRNA were analyzed by qPCR. All data was analyzed using SPSS version 22 and CFX96 manager software for comparative gene analysis. Results: The relative mRNA expression levels of AKT, PI3K, PDK1, NFkB, and mTOR were high (2.14, 1.93, 1.93, 3.31, and 1.82 folds, respectively) as compared to healthy controls, whereas expression of PTEN was down-regulated (0.10-fold) in patients. There was a significant difference (p = 0.0019) in serum levels of phosphorylated-Akt in patients and controls. The expression of miR-29b was up-regulated in patients of ovarian cancer. Conclusion: Gene expression of PTEN/AKT pathway is deregulated in ovarian cancer patients. Moreover, the phosphorylated level of AKT, expression of mTOR or miRNAs may be a marker for the disease.

Keywords

• Ovarian cancer (OC)
• miRNA (micro RNA)
• Phosphoinositide3-kinase (PI3K)
• Phosphatase and tensin (PTEN)
• Pyrunate deghydrogenase kinase 1(PDK1)