Identification of the dopamine transporter SLC6A3 as a biomarker for patients with renal cell carcinoma
MOLECULAR CANCER
Authors: Schroedter, Sarah; Braun, Martin; Syring, Isabella; Kluemper, Niklas; Deng, Mario; Schmidt, Doris; Perner, Sven; Mueller, Stefan C.; Ellinger, Joerg
Abstract
Background: Clear cell renal cell carcinoma (ccRCC) is among the most common human malignancies. Methods: In order to provide better understanding of the molecular biology of ccRCC and to identify potential diagnostic/prognostic biomarker and therapeutic targets, we utilized a microarray to profile mRNA expression of corresponding normal and malignant renal tissues. Real-time PCR, Western Blot and immunohistochemistry were applied to study the expression of candidate biomarkers. ccRCC cell lines were treated with sertraline to inhibit the dopamine transporter SLC6A3. Results: Differential expression of fourteen mRNAs, yet not studied in ccRCC in depth, was confirmed using qPCR (upregulation: SLC6A3, NPTX2, TNFAIP6, NDUFA4L2, ENPP3, FABP6, SPINK13; downregulation: FXYD4, SLC12A1, KNG1, NPHS2, SLC13A3, GCGR, PLG). Up-/downregulation was also confirmed for FXYD4, KNG1, NPTX2 and SLC12A1 by Western Blot on the protein level. In contrast to the mRNA expression, protein expression of the dopamine transporter SLC6A3 was lower in ccRCC compared to normal renal tissue. Immunohistochemistry indicated that this decrease was due to higher concentrations of SLC6A3 in the proximal tubules. Immunohistochemical analyses further demonstrated that high SLC6A3 expression in ccRCC tissue was correlated with a shorter period of recurrence-free survival following surgery. Treatment of ccRCC cells with the SLC6A3 inhibitor sertraline induced dose-dependent cell-death. Conclusion: Our study identified several novel biomarkers with diagnostic potential and further investigations on sertraline as therapeutic agent in ccRCC patients are warranted.
Bioinformatic analysis of differentially expressed genes involved in the hepatitis B virus-associated acute liver failure
ACTA GASTRO-ENTEROLOGICA BELGICA
Authors: Yong, Lv; Guang, Bai; Yan, Li
Abstract
Background : The rarity of acute liver failure, along with its severity and heterogeneity, has resulted in a very limited evidence to understand of the molecular mechanism. To analyze the differentially expressed genes (DEGs) in the Hepatitis B Virus-Associated Acute Liver Failure and elucidate the biological significance of the DEGs. Methods : Firstly, differentially expressed genes (DEGs) between seventeen HBV-associated acute liver failure liver samples and ten control normal liver samples were identified by R package. Then, the enriched GO terms and KEGG pathways of those DEGs were obtained using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Finally, protein-protein interactions (PPI) network of those DEGs were constructed using STRING database and visualized by Cytoscape software. Results : A total of 328 DEGs were identified in Hepatitis B Virus-Associated Acute Liver Failure group compared with the control group. Several novel biomarkers that might play important roles in HBV-associated acute liver failure were identified through the analysis of gene microarray in GEO. Furthermore, DEGs with high connectivity degrees, such as KNG1, PLG, F2 and pathways such as complement and coagulation cascades were noticed. Conclusion : DEGs with high connectivity degrees, such as KNG1,PLG and their relative pathway complement and coagulation cascades may be important for further understanding of the molecular mechanism of HBV-associated acute liver failure.