BackgroundLong 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.MethodsIn 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.ResultsLINC00355, 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.ConclusionTranscript levels of lncRNAs in urinary exosomes are potential diagnostic bio-markers in bladder cancer.

Schizophrenia as a common disabling psychiatric disorder has been associated with dysregulation of several genes and pathways among them are those being regulated by long non-coding RNAs (lncRNAs). Based on the acknowledged roles of lncRNAs in neurodevelopment, in the current study, we assessed expression of six lncRNAs namely HOXA-AS 2, Linc-ROR , MALAT1 , MEG3 , SPRY4-IT1 and UCA1 in peripheral blood of 60 patients with schizophrenia and 60 healthy subjects. HOXA-AS2 , Linc-ROR , MEG3 , SPRY4-IT1 and UCA1 levels were significantly higher in total patients compared with total controls. However, when evaluating expression of genes in sex-based subgroups, the differences in the expression of these lncRNAs were significant only among females. Assessment of partial correlation between expression of lncRNAs and age of study participants after controlling the effect of sex, revealed significant correlations for HOXA-AS2 , MALAT1 and UCA1 in both patients and controls. Besides, expressions of Linc-ROR and SPRY4-IT1 were correlated with age only in patients. Significant pairwise correlations were recognized between expression levels of lncRNAs in both patients with schizophrenia and controls. Based on the area under curve (AUC) values, SPRY4-IT1 had the best performance in differentiation of female patients with schizophrenia from female controls (AUC = 0.85, P < 0.0001). Combination of Linc-ROR , MEG3 , SPRY4-IT1 and UCA1 expression levels could differentiate female patients with 95.2% sensitivity, 76.9% specificity and diagnostic power of 0.88 (P < 0.0001). The current study suggests the presence of a sex-based dysregulation of lncRNAs in patients with schizophrenia and their possible application as diagnostic biomarkers.

BackgroundThe suppressor of cytokine signaling (SOCS) family of proteins are inhibitors of the cytokine-activated Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway. We aimed at evaluation of expression of SOCS genes in breast cancer.MethodsWe evaluated expression of SOCS1–3 and SOCS5 genes in breast cancer samples compared with the corresponding adjacent non-cancerous tissues (ANCTs).ResultsAll assessed SOCS genes were significantly downregulated in tumoral tissues compared with ANCTs. SOCS1 and SOCS2 genes were significantly overexpressed in higher grade samples, but SOCS3 had the opposite trend. Significant correlations were found between expression levels of SOCS genes. The SOCS1 and SOCS2 expression levels had the best specificity and sensitivity values respectively for breast cancer diagnosis.ConclusionThe current study provides further evidence for contribution of SOCS genes in breast cancer.

PurposeVitamin D receptor (VDR) signaling pathway is implicated in the pathogenesis of breast cancer.Patients and methodsWe selected VDR-associated long noncoding RNAs (lncRNAs) through an in silico analysis of available microarray and RNA-sequencing data and assessed their expression in 75 breast tumor samples and their adjacent noncancerous tissues (ANCTs). We also genotyped two functional polymorphisms within VDR gene in all patients.ResultsVDR, MALAT1, and LINC00511 were significantly upregulated in tumoral tissues compared with ANCTs (fold change [FC] =1.85, P=0.03; FC =1.54, P=0.04; and FC =4.75, P=0.000, respectively). In patients younger than 55 years, significant associations were found between expression levels of both SNHG16 and LINC00511 genes and nuclear grade (P=0.03), expression of LINC00346 and tubule formation (P=0.01), expression of both SNHG16 and SNHG6 genes and family history of cancer (P=0.01 and 0.03, respectively), as well as expression of VDR and progesterone receptor status (P=0.03). We detected significant correlations between expression levels of VDR and SNHG16 in both tumoral tissues and ANCTs. The TT genotype of FokI polymorphism was associated with the higher expression levels of VDR. FokI variants were associated with expression levels of both MALAT1 and SNHG16 in ANCTs (P=0.01 and 0.03, respectively). CdxII variants were associated with expression levels of SNHG16 in ANCTs. A significant correlation was found between FC values of SNHG16 expression and vitamin D levels.ConclusionThe present study provides further evidence for the contribution of VDR signaling and the related lncRNAs in the pathogenesis of breast cancer and introduces some novel lncRNAs as putative molecules in the interactive functional network of VDR signaling in breast cancer.

BackgroundExosomes have been regarded as emerging tools for cancer diagnosis. Tumor-derived exosomes contain molecules that enhance cancer progression and affect immune responses.Material and methodsIn 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.ResultsExosomal 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.ConclusionThe 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.

Background Plasma circulating cell-free (cf) DNA is regarded as a source of tumor DNA. Based on availability of blood tissue for the purposes of early detection of cancer and patients’ follow-up, several studies have evaluated concentration of cf DNA in cancer patients in association with tumor features. In the present study, we assessed concentration of cf DNA in lung cancer patients with two commercial kits (MN and QIAGEN) to find whether it can be used as a prognostic biomarker. Results Primary cf DNA concentrations as measured by QIAGEN kit was significantly higher in patients who died in the follow-up period compared with alive patients (P = 0.007). Moreover, the concentrations as measured by both methods were higher in patients who experienced recurrence in the follow-up period compared with patients without recurrence (P = 0.008 and 0.007 for MN and QIAGEN kits respectively). Significant associations were also found between cf DNA concentrations and tumor stage (P = 0.005 and 0.02 for MN and QIAGEN kits respectively). Notably, cf DNA concentration was higher in metastatic tumors compared with non-metastatic tumors in association with number of involved organs. Based on the AUC values, both kits could differentiate metastatic cancers from non-metastatic ones with accuracy of 98%. Conclusions The current study highlights the accuracy of cf DNA concentrations for prediction of disease course in lung cancer patients.

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