Identification of key genes in glioblastoma-associated stromal cells using bioinformatics analysis.

The aim of the present study was to identify key genes and pathways in glioblastoma-associated stromal cells (GASCs) using bioinformatics. The expression profile of microarray GSE24100 was obtained from the Gene Expression Omnibus database, which included the expression profile of 4 GASC samples and 3 control stromal cell samples. Differentially expressed genes (DEGs) were identified using limma software in R language, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis of DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery software. In addition, a protein-protein interaction (PPI) network was constructed. Subsequently, a sub-network was constructed to obtain additional information on genes identified in the PPI network using CFinder software. In total, 502 DEGs were identified in GASCs, including 331 upregulated genes and 171 downregulated genes. Cyclin-dependent kinase 1 (CDK1), cyclin A2, mitotic checkpoint serine/threonine kinase (BUB1), cell division cycle 20 (CDC20), polo-like kinase 1 (PLK1), and transcription factor breast cancer 1, early onset (BRCA1) were identified from the PPI network, and sub-networks revealed these genes as hub genes that were involved in significant pathways, including mitotic, cell cycle and p53 signaling pathways. In conclusion, CDK1, BUB1, CDC20, PLK1 and BRCA1 may be key genes that are involved in significant pathways associated with glioblastoma. This information may lead to the identification of the mechanism of glioblastoma tumorigenesis.

Urinary cell-free microRNA-106b as a novel biomarker for detection of bladder cancer.

Cell-free microRNAs (miRNAs) stably and abundantly exist in body fluids and emerging evidence suggests cell-free miRNAs as a novel class of noninvasive disease biomarkers. In this study, we hypothesized that the quantitative detection of the oncogenic miR-106b-25 cluster in urine could be a useful clinical biomarker for bladder cancer (BCa). Three members of the miR-106b-25 cluster (miR-106b, miR-93 and miR-25) were quantified by real-time RT-PCR in urine supernatant of 112 BCa patients and 78 age-matched controls. In our study, the urinary levels of miR-106b were significantly higher in BCa patients than controls (P<0.001). No significant difference was observed in the urinary levels of miR-93 and miR-25 between two groups. Furthermore, the levels of urinary miR-106b were significantly reduced in postoperative samples compared with the levels in the preoperative samples (P=0.007). With respect of clinicopathological characteristics, the level of urinary miR-106b was associated with advanced tumor stage. Receiver operating characteristic (ROC) analysis revealed that urinary miR-106b had considerable diagnostic accuracy, yielding an AUC (the areas under the ROC curve) of 0.802 with 76.8% sensitivity and 72.4% specificity in differentiating BCa from controls. In conclusion, our data indicate that urinary cell-free miR-106b might provide new complementary tumor biomarkers for BCa.

Overexpression of miR-223 correlates with tumor metastasis and poor prognosis in patients with colorectal cancer.

The purpose of the study was to investigate microRNA-223 (miR-223) expression in colorectal cancer (CRC) and its relationship with tumorigenesis and disease prognosis. Quantitative real-time PCR was used to measure levels of miR-223 in tumor samples and adjacent non-cancerous tissues from 62 patients undergoing radical resection for the treatment of CRC. The associations between miR-223 expression and patient age, sex, as well as clinicopathologic parameters, such as tumor size, differentiation, location, invasion depth, metastasis, tumor-node-metastasis (TNM) stage, and overall patient survival, were analyzed by Mann-Whitney U and Kruskal-Wallis tests. Kaplan-Meier method and Cox proportional hazards regression analyses were performed to estimate the prognostic factors for patient survival prediction. The expression of miR-223 was significantly upregulated in CRC tissues compared with adjacent non-cancerous tissues (P < 0.05). This overexpression was associated with TNM stage and lymph node and distant metastases, (P < 0.05). Moreover, Kaplan-Meier analysis demonstrated that patients with high miR-223 expression had a poorer overall survival (OS) than those with low miR-223 expression (P = 0.002). Univariate analysis revealed a statistically significant correlation between OS and miR-223 level, histology grade, metastasis and TNM stage (P < 0.001). Furthermore, miR-223 levels and histology grade were independently associated with OS (HR 0.204, 95 % CI 0.101-0.415, P < 0.05 and HR 2.252, 95 % CI 1.429-3.546, P < 0.05, respectively). The overexpression of miR-223 may play an important role in the progression of CRC and can be used as an independent factor to determine CRC prognosis.

Limited diagnostic value of microRNAs for detecting colorectal cancer: a meta-analysis.

BACKGROUND: MicroRNAs have been demonstrated to play important roles in the development and progression of colorectal cancer. Several studies utilizing microRNAs as diagnostic biomarkers for colorectal cancer (CRC) have been reported. The aim of this meta-analysis was to comprehensively and quantitatively summarize the diagnostic value of microRNAs for detecting colorectal cancer. METHODS: We searched PubMed, Embase and Cochrane Library for published studies that used microRNAs as biomarkers for the diagnosis of colorectal cancer. Summary estimates for sensitivity, specificity and other measures of accuracy of microRNAs in the diagnosis of colorectal cancer were calculated using the bivariate random effects model. A summary receiver operating characteristic (SROC) curve was also generated to summarize the overall effectiveness of the test. RESULT: Thirteen studies from twelve published articles met the inclusion criteria and were included. The overall sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odd ratio of microRNAs for the diagnosis of colorectal cancer were 0.81 (95%CI: 0.79-0.84), 0.78 (95%CI: 0.75-0.82), 4.14 (95%CI: 2.90- 5.92), 0.24 (95%CI: 0.19-0.30), and 19.2 (95%CI: 11.7-31.5), respectively. The area under the SROC curve was 0.89. CONCLUSIONS: The current evidence suggests that the microRNAs test might not be used alone as a screening tool for CRC. Combining microRNAs testing with other conventional tests such as FOBT may improve the diagnostic accuracy for detecting CRC.