Abstract
Ovarian cancer is the most common gynecological malignancy and constitutes the fifth leading cause of female cancer death. Some biological parameters have prognostic roles in patients with advanced ovarian cancer and their expression may contribute to tumor progression. The aim of this study was to investigate the potential prognostic value of SKP2, genes P27Kip1, K-ras, c-Myc, COX2 and HER2 genes expression in ovarian cancer. This study was performed on two hundred formalin fixed paraffin embedded ovarian cancer and normal adjacent tissues (NAT). Gene expression levels were assessed using real time PCR and Western blotting. Elevated expression levels of SKP2, K-ras, c-Myc, HER2 and COX2 genes were observed in 61.5% (123/200), 92.5% (185/200), 74% (148/200), 96 % (192/200), 90% (180/200) and 78.5% (157/200) of cancer tissues, respectively. High expression of SKP2 and down-regulation of P27 was associated with advanced stages of cancer. The association between high expression of c-Myc and SKP2 with low expression of P27 suggested that the Skp2-P27 pathway may play an important role in ovarian carcinogenesis. Reduced expression of P27 is associated with advanced stage of cancer and can be used as a biological marker in clinical routine assessment and management of women with advanced ovarian cancer.
Highlights
Ovarian cancer is the fifth leading cause of cancer death worldwide
The aberrant expression of S-phase kinase protein 2 (Skp2) during cell cycle can promote S-phase entry associated with loss of p27Kip1.Previous studies suggest that Skp2 expression may play a significant role in the etiology and pathogenesis of a number of systemic malignancies and associated with decreased survival probability rates and a worse clinical outcome (Ben-Izhak et al, 2009; Wang et al, 2012). p27Kip1, a key cell cycle inhibitor, is a cdk3 inhibitor that regulates progression from G1 into S-phase by inhibiting a variety of cyclin/cdk complexes, including cyclin D/cdk4, cyclin E/cdk2, and cyclin A/cdk2 (MacLachlan et al, 1995)
Overexpression of Skp2 has been reported in several malignant tumors, including hepatocellular carcinoma (Zhang et al, 2002), colorectal carcinoma (Li et al, 2004),oral squamous cell carcinoma (Shintani et al, 2003), and ovarian cancer (Shigemasa et al, 2003)
Summary
Ovarian cancer is the fifth leading cause of cancer death worldwide. It is one of the worst prognoses among gynecologic malignancies with ~90% of cancers arise are carcinomas (Ozols, 1992; Auersperg et al, 2001; Poorolajal et al, 2014). P27Kip inhibits most cyclin/Cdk complexes, in particular cyclin E/Cdk and its expression causes cell cycle arrest in G1 phase, while its loss increase rate of cell proliferation (Hulit et al, 2006). The overexpression of Skp may play an important role in the pathogenesis of ovarian cancer as well, and assessed the significance of its expression with p27Kip as a predictive marker for the prognosis of primary cases of this disease. Results: Elevated expression levels of SKP2, K-ras, c-Myc, HER2 and COX2 genes were observed in 61.5% (123/200), 92.5% (185/200), 74% (148/200), 96 % (192/200), 90% (180/200) and 78.5% (157/200) of cancer tissues, respectively. High expression of SKP2 and down-regulation of P27 was associated with advanced stages of cancer. Reduced expression of P27 is associated with advanced stage of cancer and can be used as a biological marker in clinical routine assessment and management of women with advanced ovarian cancer
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