MDM2 protein is well known as an antagonist of tumorsuppressor protein TP53. However, other MDM2-associated genes are still not investigated comprehensively. The aim of the study was therefore to identify new MDM2-associated genes. After inhbition of MDM2 in the soft tissue sarcoma (STS) cell line A204, we could identify in microarray studies eight genes more than 2fold upregulated and 101 genes were more than 2fold downregulated. Out of the downregulated genes we investigated for two genes - Piwi-like and CD26 - the prognostic relevance of mRNA expression for STS-patients. We examined 64 frozen primary tumour samples from 64 adult STS patients (before an adjuvant treatment) by quantitative RT-PCR for mRNA expression. The results of qRT-PCR were normalized for HPRT mRNA expression. In multivariate Cox-regression analyses we found (1) high level expression of Piwi-like in STS is a significant prognostic factor (P=0.038) with a 3.4-fold increased risk of tumor related death compared to patients whose tumors possessed a moderate level of HIWI expression, (2) moderate expression of CD26 was correlated with a 3.1-fold risk of tumor related death (P=0.046) compared to patients with low CD26 mRNA expression. Piwi-like is known already to play a role in male germ-cell tumours, i.e. seminomas, and CD26 can have a role in tumor progression such as cell adhesion, invasion, and cell cycle arrest. However, this is the first report showing that mRNA expression of Piwi-like and CD26 is significantly correlated to prognosis of STS patients.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]