Diagnostic Value of microRNA-375 as Future Biomarker for Prostate Cancer Detection: A Meta-Analysis.

Background and Objectives: Responding to the need for additional biomarkers for the diagnosis of prostate cancer (PCa), mounting studies show that microRNAs (miRNAs/miRs) possess great potential as future promising diagnostic tools. However, the usefulness of these miRNAs is still highly debated, as the degree of inconsistency between study designs and results is still elevated. Herein, we present a meta-analysis evaluating the diagnostic value and accuracy of circulating miR-375, as it is one of the most studied types of miRs in PCa. Materials and Methods: The diagnostic accuracy of miR-375 was evaluated using the QUADAS-2 tool, analyzing different statistical parameters. The seven studies (from six articles) that matched our selection included 422 PCa patients and 212 controls (70 healthy volunteers + 142 with benign prostate diseases). Results and Conclusion: We obtained a p-value of 0.76 for sensitivity, 0.83 for specificity, 16 for DOR, 4.6 for LR+, 0.29 for LR-, and 0.87 for AUC (95% CI 0.83-0.89). Our results confirm that miRNA-375 has high diagnostic potential for PCa, suggesting its usefulness as a powerful biomarker. More comprehensive studies are warranted to better assess its true value as a diagnostic biomarker for this urologic disease.

Cognitive dysfunction in young subjects with periodontal disease.

BACKGROUND: Periodontal disease is an inflammatory, dysbiotic condition. Studies have shown that in the elderly, periodontal disease was associated with cognitive dysfunction and Alzheimer's disease. OBJECTIVE: To investigate whether young healthy subjects with periodontal disease have lower cognition compared to those without periodontal disease. The salivary cytokines (IL-1ß, TNF-α) levels in relation to cognition were also tested. METHODS: In a monocenter, cross-sectional study, forty subjects [mean age (SD) = 34 (5) and 48% female] from western Romania were classified into periodontal disease conditions using radiographic assessment: 10 subjects had aggressive periodontitis (AGG_P), 20 chronic mild-moderate periodontitis (CR_P), and 10 no periodontitis (NL_P). Neuropsychological assessment performed by standardized neurologists and psychologist included Rey Auditory Verbal Learning Test (RAVLT), Montreal Cognitive Assessment test (MOCA), Mini-Mental State Examination (MMSE), and Prague tests. Salivary cytokines levels were determined by ELISA. RESULTS: RAVLT and MOCA delayed recall scores were lower in AGG_P group compared to NL_P and CR_P. The learning curve was also different with subjects with AGG_P showing reduced learning performance. Contrary to our hypothesis, salivary IL-1ß associated with immediate but not delayed cognitive scores. CONCLUSIONS: These results showed for the first time that subjects with AGG_P had cognitive dysfunction and IL-1ß may play a role in this process.

Long Non-Coding RNA Expression in Laser Micro-Dissected Luminal A and Triple Negative Breast Cancer Tissue Samples-A Pilot Study.

Background and Objectives: Breast cancer (BC) remains one of the major causes of cancer death in women worldwide. The difficulties in assessing the deep molecular mechanisms involved in this pathology arise from its high complexity and diverse tissue subtypes. Long non-coding RNAs (lncRNAs) were shown to have great tissue specificity, being differentially expressed within the BC tissue subtypes. Materials and Methods: Herein, we performed lncRNA profiling by PCR array in triple negative breast cancer (TNBC) and luminal A tissue samples from 18 BC patients (nine TNBC and nine luminal A), followed by individual validation in BC tissue and cell lines. Tissue samples were previously archived in formalin-fixed paraffin-embedded (FFPE) samples, and the areas of interest were dissected using laser capture microdissection (LCM) technology. Results: Two lncRNAs (OTX2-AS1 and SOX2OT) were differentially expressed in the profiling analysis (fold change of 205.22 and 0.02, respectively, p < 0.05 in both cases); however, they did not reach statistical significance in the individual validation measurement (p > 0.05) when analyzed with specific individual assays. In addition, GAS5 and NEAT1 lncRNAs were individually assessed as they were previously described in the literature as being associated with BC. GAS5 was significantly downregulated in both TNBC tissues and cell lines compared to luminal A samples, while NEAT1 was significantly downregulated only in TNBC cells vs. luminal A. Conclusions: Therefore, we identified GAS5 lncRNA as having a differential expression in TNBC tissues and cells compared to luminal A, with possible implications in the molecular mechanisms of the TNBC subtype. This proof of principle study also suggests that LCM could be a useful technique for limiting the sample heterogeneity for lncRNA gene expression analysis in BC FFPE tissues. Future studies of larger cohort sizes are needed in order to assess the biomarker potential of lncRNA GAS5 in BC.

Biomarker Potential of Plasma MicroRNA-150-5p in Prostate Cancer.

Background and Objectives: Over decades, prostate cancer (PCa) has become one of the leading causes of cancer mortality in men. Extensive evidence exists that microRNAs (miRNAs or miRs) are key players in PCa and a new class of non-invasive cancer biomarkers. Materials and Methods: We performed miRNA profiling in plasma and tissues of PCa patients and attempted the validation of candidate individual miRs as biomarkers. Results: The comparison of tissue and plasma profiling results revealed five commonly dysregulated miRs, namely, miR-130a-3p, miR-145-5p, miR-148a-3p, miR-150-5p, and miR-365a-3p, of which only three show concordant changes-miR-130a-3p and miR-150-5p were downregulated and miR-148a-3p was upregulated in both tissue and plasma samples, respectively. MiR-150-5p was validated as significantly downregulated in both plasma and tissue cancer samples, with a fold change of -2.697 (p < 0.001), and -1.693 (p = 0.035), respectively. ROC analysis showed an area under the curve (AUC) of 0.817 (95% CI: 0.680-0.995) for plasma samples and 0.809 (95% CI: 0.616-1.001) for tissue samples. Conclusions: We provide data indicating that miR-150-5p plasma variations in PCa patients are associated with concordant changes in prostate cancer tissues; however, given the heterogeneous nature of previous findings of miR-150-5p expression in PCa cells, additional future studies of a larger sample size are warranted in order to confirm the biomarker potential and role of miRNA-150-5p in PCa biology.

Distribution of microRNAs associated with major depressive disorder among blood compartments.

OBJECTIVE: Major depressive disorder (MDD) is a recurrent disorder with an increasing incidence. Alterations in key signaling pathways of the nervous system, such as the Wnt and MAPK pathways, mediated through microRNAs (miRNAs) provide crucial information regarding the etiopathology of MDD. We aimed to analyze whether the heterogeneity of literature findings regarding differential expression of miRNAs in the blood could arise from their different distributions among blood compartments. METHODS: We performed a pilot study analyzing the differential expression of miR-26a, miR-494, miR-30c, miR-93, and miR-101 and investigated their levels in white blood cells, total plasma (TP), exosomes from plasma, and exosome depleted plasma (EDP) in patients with MDD before and after antidepressant treatment with escitalopram and in healthy controls. RESULTS: MiR-494 was more abundant in EDP, and miR-26a and miR-30c were predominantly more abundant in TP relative to other blood compartments. Moreover, miR-30c, miR-101, and miR-26a, were significantly downregulated in TP of patients with MDD compared with controls. After antidepressant treatment, only miR-494 was significantly differently expressed in EDP. CONCLUSIONS: This proof-of-principle study suggests that identifying the miRNA abundance in different blood compartments is crucial for biomarker development and could enrich the current knowledge regarding MDD pathophysiology.

Long Noncoding RNA NEAT1 as a Potential Candidate Biomarker for Prostate Cancer.

Background: Prostate cancer (PCa) remains one of the leading causes of cancer-related mortality in men worldwide, mainly due to unsatisfactory diagnostic methods used at present, which lead to overdiagnosis, unnecessary biopsies and treatment, or misdiagnosis in early asymptomatic stages. New diagnostic biomarkers are needed for a correct and early diagnosis. Long noncoding RNAs (lncRNAs) have been broadly studied for their involvement in PCa biology, as well as for their potential role as diagnostic biomarkers. Methods: We conducted lncRNA profiling in plasma and microdissected formalin-fixed paraffin-embedded (FFPE) tissues of PCa patients and attempted validation for commonly dysregulated individual lncRNAs. Results: Plasma profiling revealed eight dysregulated lncRNAs, while microarray analysis revealed 717 significantly dysregulated lncRNAs, out of which only nuclear-enriched abundant transcript 1 (NEAT1) was commonly upregulated in plasma samples and FFPE tissues. NEAT1's individual validation revealed statistically significant upregulation (FC = 2.101, p = 0.009). Receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) value of 0.7298 for NEAT1 (95% CI = 0.5812-0.8785), suggesting a relatively high diagnostic value, thus having a potential biomarker role for this malignancy. Conclusions: We present herein data suggesting that NEAT1 could serve as a diagnostic biomarker for PCa. Additional studies of larger cohorts are needed to confirm our findings, as well as the oncogenic mechanism of NEAT1 in the development of PCa.

A preliminary study of microRNA expression in different types of primary melanoma.

MicroRNAs (miRNAs) have been proven to regulate the development and progression of cancer through various mechanisms. The aim of the present study was to compare miRNA expression between primary melanomas from different sites. We analyzed the expression of 84 miRNAs in 27 primary melanoma and 5 nevus formalin-fixed paraffin-embedded (FFPE) samples using the Human Cancer PathwayFinder miScript miRNA PCR Array. The FFPE samples were obtained from the archives of the Municipal Clinical Emergency Hospital of Timisoara and included 10 cutaneous melanomas, 10 uveal melanomas, 7 mucosal melanomas, and 5 cutaneous nevi. Out of 84 miRNAs, 11 miRNAs showed altered expression in all types of melanoma compared with the nevi. Among these, miR-155-5p, miR-9-5p, miR-142-5p, miR-19a-3p, miR-134-5p, and miR-301a-3p were upregulated, while miR-205-5p, miR-203a-3p, miR-27b-3p, miR-218-5p, and miR-23b-3p were downregulated. The highest similarity in miRNA expression pattern was found between uveal and mucosal melanoma groups, i.e., 15 miRNAs had altered expression in both groups. Overall, we identified several miRNAs with significantly altered expression in primary melanomas, including those reported for the first time in this type of cancer. Among them, mir-9-5p, mir-203a-3p, mir-19a-3p, mir-27b-3p, and mir-218-5p showed altered expression in all three melanoma types vs. nevi. Further research should explore the potential of these miRNAs in melanoma.

Changes in global DNA methylation and hydroxymethylation in oral mucosa according to tobacco smoke exposure.

OBJECTIVE: This prospective clinical study comparatively investigated the effects of tobacco smoking on global methylation and hydroxymethylation in oral epithelial cells. METHODS: Buccal cells from the inside of the cheeks were collected from 47 individuals, including smokers, former smokers, and never smokers. DNA was extracted using dedicated kits. Methylated and hydroxymethylated DNA fractions were measured using assays similar to enzyme-linked immunosorbent assays. The levels of methylation and hydroxymethylation were compared among groups using unpaired two-tailed t-tests or the Mann-Whitney U test; P < 0.05 was considered statistically significant. RESULTS: There was no statistically significant difference in the average number of cigarettes between smoker and former smoker groups. Although methylation levels were lower for smokers (3.1%) and former smokers (2.16%), compared with never smokers (4.16%), these differences were not statistically significant. There was a two-fold increase in hydroxymethylation level in never smokers, compared with smokers. CONCLUSIONS: Our findings suggest that smoking leads to global reductions in both methylation and hydroxymethylation levels in oral epithelial cells in a manner influenced by the intensity and length of exposure to tobacco smoke.