Urinary exosomal expression of long non-coding RNAs as diagnostic marker in bladder cancer

Fatemeh Yazarlou,1 Mohammad Hossein Modarressi,1 Seyed Javad Mowla,2 Vahid Kholghi Oskooei,3 Elahe Motevaseli,4 Leila Farhady Tooli,5 Leila Nekoohesh,6 Maryam Eghbali,1 Soudeh Ghafouri-Fard,3 Mandana Afsharpad7 1Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 2Faculty of Biological Sciences, Department of Genetics, Tarbiat Modares University, Tehran, Iran; 3Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 5Department of Microbiology, School of Biology, College of Science, Tehran University, Tehran, Iran; 6Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 7Cancer Control Research Center, Cancer Control Foundation, Iran University of Medical Sciences, Tehran, Iran Background: Long non-coding RNAs (lncRNAs) and exosomes have been regarded as components of cell signal transmission that modulate indigenous cellular microenvironments. Exosomes also participate in relocation of functional lncRNAs between cells. Methods: In the present study, we evaluated expression of LINC00355, LINC00958, UCA1-201, UCA1-203, and MALAT1 lncRNAs in urinary exosomes isolated from transitional cell carcinoma (TCC) of bladder, non-malignant urinary disorders, and normal subjects. Results: LINC00355, UCA1-203, and MALAT1 expression was significantly higher in TCC patients compared to controls (non-malignant or normal samples). However, UCA1-201 expression was significantly decreased in TCC patients compared with controls. LINC00355 and MALAT1 expression was significantly lower in cigarette smokers and opium-addicted TCC patients, respectively. On the other hand, LINC00355 expression tended to be higher in opium-addicted TCC patients. The proposed panel of lncRNAs (composed of UCA1-201, UCA1-203, MALAT1, and LINC00355) had 92% sensitivity and 91.7% specificity for diagnosis of bladder cancer from normal samples. Conclusion: Transcript levels of lncRNAs in urinary exosomes are potential diagnostic biomarkers in bladder cancer. Keywords: lncRNA, exosome, bladder cance

Urine exosome gene expression of cancer-testis antigens for prediction of bladder carcinoma

Fatemeh Yazarlou,1 Seyed Javad Mowla,2 Vahid Kholghi Oskooei,3 Elahe Motevaseli,4 Leila Farhady Tooli,5 Mandana Afsharpad,6 Leila Nekoohesh,7 Nafiseh Sadat Sanikhani,4 Soudeh Ghafouri-Fard,3 Mohammad Hossein Modarressi1 1Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 2Faculty of Biological Sciences, Department of Genetics, Tarbiat Modares University, Tehran, Iran; 3Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 5Department of Microbiology, School of Biology, College of Science, Tehran University, Tehran, Iran; 6Cancer Control Research Center, Cancer Control Foundation, Iran University of Medical Sciences, Tehran, Iran; 7Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran Background: Exosomes have been regarded as emerging tools for cancer diagnosis. Tumor-derived exosomes contain molecules that enhance cancer progression and affect immune responses. Material and methods: In the present study, we evaluated expression of seven cancer-testis antigens (CTAs) that are regarded as putative biomarkers and immunotherapeutic targets along with NMP22 in urinary exosomes of bladder cancer patients, healthy subjects and patients affected with nonmalignant urinary disorders. Results: Exosomal expression of MAGE-B4 was significantly higher in bladder cancer patients compared with normal samples (expression ratio=2.68, P=0.01). However, its expression was lower in bladder cancer patients compared with benign prostate hyperplasia (BPH) patients (expression ratio=0.17, P=0.01). Exosomal expression of NMP22 was significantly higher in bladder cancer patients compared with BPH patients (expression ratio=9.22, P=0.02). Expressions of other genes were not significantly different between bladder cancer patients and normal/nonmalignant samples. We found significant correlation between MAGE-A3 and MAGE-B4 expressions in exosomes obtained from controls. In addition, TSGA10 expression was correlated with expression of NMP22 in both cancer patients and controls. Conclusion: The present study provides evidences for differential expression of CTAs in urinary exosomes of bladder cancer patients and urogenital disorders and warrants further studies for assessment of their significance in cancer diagnosis and immunotherapeutic approaches. Keywords: cancer-testis antigen, bladder cancer, exosom