Abstract 237: Piwi genes and tissue/serum piR-651 are related to clinicopathologic features of renal cell carcinoma
Authors: Robert Iliev, Petra Vychytilova-Faltejskova, Jaroslav Juracek, Hana Mlcochova, Michal Stanik, Jan Dolezel, Michal Fedorko, Dalibor Pacik, Marek Svoboda, Ondrej Slaby
Journal: Cancer Research (2015)

Abstract Introduction: Piwi-interacting RNAs (piRNAs) consists a newly discovered class of non-coding RNA. PiRNAs were first identified in the germ cells of various animal species. They bind to Piwi proteins which are a subfamily of Argonaut proteins. In humans were identified four Ago genes and four Piwi genes. Human Piwi genes include PIWIL1, PIWIL2, PIWIL3 and PIWIL4. Recent studies suggest that deregulated expression of Piwi proteins is common to many types of tumors and also correlate with clinicopathologic features and worse prognosis in patients with breast, cervical, ovarian, colorectal and other cancers. PiRNAs are short single-stranded RNAs with 26-31 nucleotides in length. They are involved in silencing of transposable elements and it is assumed that also participate in sequence-specific chromatin modifications. The differential expression of piRNAs was found in gastric and breast cancer. In our pilot study we analyzed expression of Piwi genes and piR-651, which was previously found to be deregulated in various types of tumors. Patients and Methods: In our study, we have used the tumor tissue and the paired renal parenchyma tissue of 56 patients with renal cell carcinoma (RCC). From the tissue was isolated total RNA and by RT-qPCR were examined the expression of Piwi genes and piR-651. For the analysis of circulating piR-651, blood serum samples of 75 patients with RCC and 75 age, gender-matched healthy donors were used. We have compared expression levels of the studied genes in tumor and non-tumor tissues, serum samples, and also correlated them with clinicopathologic features of RCC patients (stage, grade, RFS, OS). Results: We found a significant down-regulation of PIWIL1 (p&amp;lt;0,0001) and piR-651 (p&amp;lt;0,0001) expression levels in tumor tissue when compared to paired renal parenchyma samples. The expression levels of PIWIL2, PIWIL3 and PIWIL4 were not significantly deregulated in tumor tissue. Interestingly, levels of PIWIL2 and PIWIL4 correlated significantly with the stage (p = 0,002 and p = 0,003, resp.) and grade (p = 0.007 and p&amp;lt;0.0001, resp.) of RCC. We found also a correlation between higher levels of PIWIL1 and overall survival (p&amp;lt;0.05). We have observed significantly decreased expression levels of piR-651 in blood serum samples of RCC patients when compared to healthy donors and accordingly to ROC analysis we were able to distinguish blood serum of RCC patients and control subjects with the sensitivity of 77.33% and a specificity of 72.37%. Expression levels of serum piR-651 were not in correlation with the stage and grade of RCC. Conclusion: Accordingly to our pilot data expression of Piwi genes is altered in tumor tissue and is correlated to selected clinicopathologic features of RCC. We also suggest the potential of piR-651 in blood serum as novel non-invasive diagnostic biomarker in RCC. Acknowledgments: IGA MZCR No: NT/13860-4/2012, NT/13549-4/2012, NT/13547-4/2012, NT/13514-4/2012 Citation Format: Robert Iliev, Petra Vychytilova-Faltejskova, Jaroslav Juracek, Hana Mlcochova, Michal Stanik, Jan Dolezel, Michal Fedorko, Dalibor Pacik, Marek Svoboda, Ondrej Slaby. Piwi genes and tissue/serum piR-651 are related to clinicopathologic features of renal cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 237. doi:10.1158/1538-7445.AM2015-237