Exosomal miRNA Expression Profiling and the Roles of Exosomal miR-4741, miR-32, miR-3149, and miR-6727 on Gastric Cancer Progression.

Objective: Accumulated evidence highlights the biological implications of exosomes in gastric cancer. Herein, we conducted the exosomal miRNA expression profiling and identified potential diagnostic markers for gastric cancer. Methods: Plasma exosomes were isolated and identified from three gastric cancer patients and three healthy participants. Microarrays of exosomal miRNAs were then analyzed. Differentially expressed exosomal miRNAs were screened with fold - change|≥2.0 and p ≤ 0.05. Among them, miR-4741, miR-32, miR-3149, and miR-6727 expressions were verified in tissues and plasma of patients and healthy subjects. ROC curves were conducted for evaluating the diagnostic performance. The roles of miR-32, miR-3149, miR-6727, and miR-4741 on gastric cancer progression were observed by cellular experiments. Results: Isolated exosomes were well characterized by Western blot and transmission electron microscopy as well as nanoparticle-tracking analyses. According to the microarrays, 142 exosomal miRNAs were upregulated, and 34 were downregulated in gastric cancer than healthy subjects. miR-4741 upregulation and miR-32, miR-3149, and miR-6727 downregulations were found in tissues and plasma of gastric cancer patients. The AUCs of miR-4741, miR-32, miR-3149, and miR-6727 were separately 0.8554, 0.9456, 0.7683, and 0.8923. Upregulated miR-32, miR-3149, and miR-6727 as well as downregulated miR-4741 lowered proliferative, migratory, and invasive capacities as well as elevated apoptotic levels of gastric cancer cells. Conclusion: Our study successfully isolated and verified exosomes from plasma of gastric cancer as well as proposed four exosomal miRNAs that could act as promising diagnostic markers and suppress gastric cancer progression.

lncRNAs as potential molecular biomarkers in the clinicopathology and prognosis of cholangiocarcinoma: a systematic review and meta-analysis.

BACKGROUND: Cholangiocarcinoma (CCA) is the second most common fatal primary hepatobiliary malignant carcinoma, characterized by early invasion and extremely poor outcomes. It is therefore necessary to identify a novel biomarker to better diagnose CAA and predict its prognosis. Recently, emerging evidence has revealed that some lncRNAs play an important role in the tumorigenesis and progression of CAA. In order to support this search for novel diagnostic and prognostic biomarkers for CAA, we conducted a meta-analysis to analyze the published association between lncRNA expression and its clinical value in CAA. METHODS: Eligible studies were pooled and analyzed according to our inclusion and exclusion criteria after a comprehensive literature search. Stata 14.0 software was used to analyze the data from relevant studies and to construct a forest plot. Different effect sizes were selected for the meta-analysis. RESULTS: In total, 24 publications were included in this meta-analysis. After review of their full-text, 16 articles studied the association between lncRNAs and clinicopathological characteristics, 2 discussing diagnosis and 16 discussing prognosis. Our results showed that overexpression of CCAT1 was significantly correlated with tumor stage (I + II vs III + IV) (OR, 4.99; 95% CI 2.77-8.99; P<0.001) and lymph node metastasis in CCA (OR, 4.75; 95% CI 2.65-8.52; P<0.001). Furthermore, elevated CCAT lncRNA family expression predicted a shorter overall survival (HR, 2.09; 95% CI 1.17-3.00; P<0.001), especially CCAT2. Upregulation of CCAT2 was also obviously associated with tumor stage in CCA (OR, 5.29; 95% CI 2.64-10.58; P=0.001). CONCLUSION: This is the first meta-analysis to assess the relationship between expression of lncRNAs and the clinical values of patients with CCA. lncRNAs can function as potential molecular biomarkers of the clinicopathology and prognosis of CCA.

LncRNA as a diagnostic and prognostic biomarker in bladder cancer: a systematic review and meta-analysis.

BACKGROUND: Bladder cancer is one of the most common urinary malignancies, and has a high recurrence rate and poor outcomes. In order to identify novel diagnostic and prognostic biomarkers for bladder cancer, we conducted a meta-analysis to analyze the association between long non-coding RNA (lncRNA) expression and survival in bladder cancer. MATERIALS AND METHODS: We searched literature from databases using our inclusion and exclusion criteria. STATA 14.0 software was used to analyze the data from collected studies and to construct the forest plots. A different effect size was selected for each meta-analysis. RESULTS: After selection, 30 articles were found to be eligible. The present meta-analysis contains data from 13 articles about clinicopathological characteristics, six articles about diagnosis, and 16 articles about prognosis. In the present study, we found that many lncRNAs could function as potential diagnostic and prognostic markers in bladder cancer. Among these findings, UCA1 was expected to be a diagnostic biomarker for bladder cancer, while the aberrant expression of HOTAIR and GAS5 was associated with poor disease-free survival/recurrence-free survival/disease-specific survival. CONCLUSION: Overall, the present study is the first meta-analysis to assess the association between expression of lncRNAs and clinical value in patients with bladder cancer. LncRNAs hold promise as novel diagnostic and prognostic markers in bladder cancer.

MicroRNA-23a/24-2/27a as a potential diagnostic biomarker for cancer: A systematic review and meta-analysis.

An increasing number of studies have proven that microRNAs play an important role in the occurrence, development and prognosis of various types of cancer. As a vital gene cluster, the microRNA (miR)-23a/24-2/27a cluster may be an important marker for predicting cancer prognosis and tumor progression. A search was conducted through PubMed, Medline and the Cochrane Library to identify studies investigating the association between the miR-23a/24-2/27a cluster and cancer, and the identified related studies were included in the present meta-analysis. The strength of the association was assessed by hazard ratio (HR) and its 95% confidence interval (95% CI). A total of 21 studies were included in this meta-analysis. The results indicated that a high level of miR-23a exerted a significant effect on overall survival (OS) (HR=2.33, 95% CI: 1.18-4.58; P=0.014), but not on disease-free survival (DFS)/recurrence-free survival (RFS) (HR=1.13, 95% CI: 0.37-3.44; P=0.836). There was an obvious statistically significant association between OS and the expression of miR-24 (HR=2.49, 95% CI: 1.84-3.37; P=0.000), particularly in the digestive system (pooled HR=2.99, 95% CI: 2.17-4.13, P=0.000). In addition, the result suggested a statistically significant association between the expression of miR-27a and OS (pooled HR=1.89, 95% CI: 1.32-2.69; P=0.001), as well as DFS/RFS/progression-free survival (HR=2.19, 95% CI: 1.29-3.70; P=0.003), particularly in renal cell carcinoma (HR=2.30, 95% CI: 1.16-4.67; P=0.017). A subgroup analysis by ethnicity, cancer type and statistical methodology was performed. There was no obvious publication bias. In conclusion, the present study demonstrated that the miR-23a/24-2/27a cluster may be a useful marker for predicting cancer prognosis and tumor progression.