Dataset Information

Circulating miR-200c as a diagnostic and prognostic biomarker for gastric cancer.

ABSTRACT: BACKGROUND: MicroRNAs are aberrantly expressed and correlate with tumourigenesis and the progression of solid tumours. The miR-200 family determines the epithelial phenotype of cancer cells and regulates invasiveness and migration. Thus, we hypothesised that the quantitative detection of the miR-200 family as epithelial-specific microRNAs in the blood could be a useful clinical biomarker for gastric cancer (GC). METHODS: We initially validated the expression levels of miR-200a, 200b, 200c and 141 in GC cell lines (n?=?2) and blood from healthy controls (n?=?19) using real-time quantitative reverse transcription PCR (qRT-PCR). The microarray expression profiles of the miR-200 family in 160 paired samples of non-tumour gastric mucosae and GC were downloaded through ArrayExpress and analysed. MiR-200c was selected for clinical validation. The qRT-PCR prospective assessment of miR-200c was performed using 67 blood samples (52 stage I-IV GC patients and 15 controls); the area under the receiver operating characteristic curve (AUC-ROC) was estimated. The Kaplan-Meier and Breslow-Wilcoxon tests were used to assess the correlation of miR-200c with overall and progression-free survival (OS and PFS). Multivariate analyses were performed using the Cox model. RESULTS: The miR-200c blood expression levels in GC patients were significantly higher than in normal controls (p?=?0.018). The AUC-ROC was 0.715 (p?=?0.012). The sensitivity, specificity and accuracy rates of 65.4%, 100% and 73.1%, respectively, were observed. The levels of miR-200c in the blood above the cutoff defined by the ROC curve was found in 17.6% of stage I-II GC patients, 20.6% of stage III patients and 67.7% of stage IV patients (p?

SUBMITTER: Valladares-Ayerbes M

PROVIDER: S-EPMC3494541 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Circulating miR-200c as a diagnostic and prognostic biomarker for gastric cancer.

Valladares-Ayerbes Manuel M Reboredo Margarita M Medina-Villaamil Vanessa V Iglesias-Díaz Pilar P Lorenzo-Patiño Maria José MJ Haz Mar M Santamarina Isabel I Blanco Moisés M Fernández-Tajes Juan J Quindós Maria M Carral Alberto A Figueroa Angélica A Antón-Aparicio Luis Miguel LM Calvo Lourdes L

Journal of translational medicine 20120906

<h4>Background</h4>MicroRNAs are aberrantly expressed and correlate with tumourigenesis and the progression of solid tumours. The miR-200 family determines the epithelial phenotype of cancer cells and regulates invasiveness and migration. Thus, we hypothesised that the quantitative detection of the miR-200 family as epithelial-specific microRNAs in the blood could be a useful clinical biomarker for gastric cancer (GC).<h4>Methods</h4>We initially validated the expression levels of miR-200a, 200b ...[more]

PMID: 22954417

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Project description:Gastric carcinoma (GC) refers to a common digestive system disease that exhibits a very high incidence. MicroRNA hsa-mir-3923 belongs to a type of miRNA, of which the function has been merely investigated in breast, pancreatic cancers and pre-neoplasic stages of gastric cancer. It has not been studied or reported in gastric carcinoma, so the relationship between gastric hsa-mir-3923 expression and the clinics feature and pathology of GC cases was examined. This study employed data mining for analyzing gastric carcinoma data in The Cancer Genome Atlas database. A Chi squared test was performed for assessing the relations of hsa-mir-3923 expression with clinics-related and pathology-regulated variables. This study conducted the assessment of the role of hsa-mir-3923 in prognostic process using Kaplan-Meier curves, Receiver operating characteristic (ROC) analysis and proportional hazards model (Cox) study. With the use of Gene Expression Omnibus, this study carried out gene set enrichment analysis (GSEA). In the meantime, the common miRNA database was compared to predict potential target genes; as revealed by co-expression analysis, a regulatory network probably existed, containing hsa-mir-3923. For the analysis of the most tightly associated cytological behavior and pathway in GC, this study adopted the databases for Annotation, Visualization and Integrated Discovery (David) and KO-Based Annotation System (KOBAS). Cytoscape, R and STRING were employed for mapping probable regulatory networks displaying relations to hsa-mir-3923. Lastly, we obtained 69 genes most tightly associated with hsa-mir-3923 and described their relationship with Circos plot. As revealed from the results, hsa-mir-3923 displayed up-regulation in gastric carcinoma, and it displayed associations with vital status, N stage and histologic grade when being expressed. The predicted results of miRNA target genes suggested that there may be a close relationship between 66 genes and hsa-mir-3923 in gastric cancer. As indicated from co-expression data, a small regulating network of 4 genes probably existed. Our results elucidated that hsa-mir-3923 high-expression reveals poor prognosis of GC patients.

Project description:Objective: This study aimed to identify the hub gene in gastric cancer (GC) tumorigenesis. A biomarker prediction model was constructed and analyzed, and protein expression in histopathological samples was verified in a validation cohort. Methods: Differentially expressed genes (DEGs) were identified from GC projects in The Cancer Genome Atlas (TCGA) database. Functional enrichment analysis of DEGs was performed between the high- and low- Ribonuclease P protein subunit p30 (RPP30) expression groups. ROC analysis was performed to assess RPP30 expression to discriminate GC from normal tissues. Functional enrichment pathways and immune infiltration of DEGs were analyzed using GSEA and ssGSEA. Survival analysis and nomogram construction were performed to predict patient survival. Immunohistochemical staining of GC tissues was performed to validate RPP30 expression in GC and paracancerous samples. Results: Gene expression data and clinical information of 380 cases (375 GC samples and 32 para-cancerous tissues) were collected from TCGA database. The AUC for RPP30 expression was found to be 0.785. The G alpha S signaling pathway was the most significantly enriched signaling pathway. Primary therapy outcome (p < 0.001, HR = 0.243, 95% CI = 0.156-0.379), age (p = 0.012, HR = 1.748, 95% CI = 1.133-2.698), and RPP30 expression (p < 0.001, HR = 2.069, 95% CI = 1.346-3.181) were identified as independent prognostic factors. As a quantitative approach, a nomogram constructed based on RPP30 expression, age, and primary therapy outcome performed well in predicting patient survival. Nineteen of the 25 tissue samples from the validation cohort showed positive RPP30 expression in GC tissues, whereas 16 cases showed negative RPP30 staining in normal tissues. The difference between the two was statistically significant. Conclusion: High RPP30 expression was significantly correlated with disease progression and poor survival in GC, promoting tumorigenesis and angiogenesis via tRNA dysregulation. This study provides new and promising insights into the molecular pathogenesis of tRNA in GC.

Dataset Information

Circulating miR-200c as a diagnostic and prognostic biomarker for gastric cancer.

Publications

Circulating miR-200c as a diagnostic and prognostic biomarker for gastric cancer.

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