scholarly journals Integrating MicroRNA Expression Profiling Studies to Systematically Evaluate the Diagnostic Value of MicroRNAs in Pancreatic Cancer and Validate Their Prognostic Significance with the Cancer Genome Atlas Data

2018 ◽  
Vol 49 (2) ◽  
pp. 678-695 ◽  
Author(s):  
Zhigang Zhang ◽  
Bing Pan ◽  
Shaocheng Lv ◽  
Zhiwei Ji ◽  
Qian Wu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mirna Expression ◽  
Expression Profiling ◽  
Target Genes ◽  
Diagnostic Value ◽  
The Cancer Genome Atlas ◽  
Systematic Evaluation ◽  
Cancer Genome Atlas ◽  
Mirna Expression Profiling ◽  
Genome Atlas

Background/Aims: MicroRNAs (miRNAs) are promising biomarkers for pancreatic cancer (PaCa). However, systemic and unified evaluations of the diagnostic value of miRNAs are lacking. Therefore, we performed a systematic evaluation based on miRNA expression profiling studies. Methods: We obtained miRNA expression profiling studies from Gene Expression Omnibus (GEO) and ArrayExpress (AE) databases and calculated the pooled sensitivity, specificity, and summary area under a receiver operating characteristic (ROC) curve for every miRNA. According to the area under the curve (AUC), we identified the miRNAs with diagnostic potentiality and validated their prognostic role in The Cancer Genome Atlas (TCGA) data. Gene Ontology (GO) annotations and pathway enrichments of the target genes of the miRNAs were evaluated using bioinformatics tools. Results: Ten miRNA expression profiling studies including 958 patients were used in this diagnostic meta-analysis. A total of 693 miRNAs were measured in more than 9 studies. The top 50 miRNAs with high predictive values for PaCa were identified. Among them, miR-130b had the best predictive value for PaCa (pooled sensitivity: 0.73 [95% confidence intervals (CI) 0.44-0.91], specificity: 0.81 [95% CI 0.59–0.93], and AUC: 0.84 [95% CI 0.73–0.95]). We identified nine miRNAs (miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301) associated with overall survival in PaCa patients by combining our results with TCGA data. The results of a Cox model revealed that two miRNAs (miR-30a [hazard ratio (HR)=2.43, 95% CI 1.05-5.59; p=0.037] and miR-203 [HR=3.14, 95% CI 1.28-7.71; p=0.012]) were independent risk factors for prognosis in PaCa patients. In total, 405 target genes of the nine miRNAs were enriched with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and cancer-associated pathways such as Ras signaling pathways, phospholipase D signaling pathway, and AMP-activated protein kinase (AMPK) signaling pathway were revealed among the top 20 enriched pathways. There were significant negative correlations between miR-181b-1 and miR-125a expression levels and the methylation status of their promoter region. Conclusion: Our study performed a systematic evaluation of the diagnostic value of miRNAs based on miRNA expression profiling studies. We identified that miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301 had moderate diagnostic value for PaCa and predicted overall survival in PaCa patients.

Analysis of Predictive Value and Target Gene Prediction of Serum Micro-RNA-205 in Diagnosis and Prognosis of Prostate Cancer

2020 ◽  
Vol 12 (2) ◽  
pp. 196-201
Author(s):  
Xiangnan Hu ◽  
Xiaoliang Dou ◽  
He Wang ◽  
Jinbo Sun ◽  
Bo Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mirna Expression ◽  
Predictive Value ◽  
Expression Profiling ◽  
Target Genes ◽  
Micro Rna ◽  
Serum Samples ◽  
Serum Mirna ◽  
Diagnosis And Prognosis ◽  
Mirna Expression Profiling

The aim of this study was to explore the predictive value of serum micro-RNA (miRNA)-205 in the diagnosis and prognosis of prostate cancer, and analyze miRNA-205 target genes and functions. Eight patients diagnosed with prostate cancer or benign prostatic hyperplasia (BPH) that were treated in January 2011 were selected. The serum samples between the two groups were analyzed for miRNA expression profiling, and the differentially expressed miRNA-205 was selected for further analysis. The serum samples of 64 patients with prostate cancer and 20 patients with BPH from March 2011 to March 2013 were collected for qPCR verification. We evaluated the correlation between miRNA-205 expression level and clinicopathological data of 64 patients with prostate cancer and its prognostic value. Finally, through bioinformatic analysis, target genes of miRNA-205 were predicted, and gene ontology (GO) analysis and signal pathway analysis were performed. A total of 657 differential miRNAs were screened from miRNA expression profiling. Compared with patients with BPH, miRNA-205 showed lower expression in the serum of patients with prostate cancer. Serum miRNA-205 + PSA combined had the strongest predictive ability, 0.805. The expression level of miRNA-205 in the patients with a Gleason score ≥7 was lower than that in patients with a Gleason score <7, Low miRNA-205 expression was associated with bone metastasis and higher T stage ratings, and the 5-year overall survival rate of the low miRNA-205 expression group was lower than the high miRNA-205 expression group. A total of 27 miRNA-205 target genes were predicted. The target genes of miRNA-205 are mainly enriched in biological functions such as cell adhesion and GTP kinase activity. The target genes of miRNA-205 are mainly enriched in Axon guidance and signal transduction by L1 and other signal pathways. In this study, serum miRNA-205 was successfully identified as a potential noninvasive serum marker for diagnosis and prognosis of prostate cancer, which will be helpful for future clinical research and prostate cancer drug target design.

scholarly journals Evaluating the Prognostic Value of microRNA-203 in Solid Tumors Based on a Meta-Analysis and the Cancer Genome Atlas (TCGA) Datasets

2017 ◽  
Vol 41 (4) ◽  
pp. 1468-1480 ◽  
Author(s):  
Yingjie Shao ◽  
Wendong Gu ◽  
Zhonghua Ning ◽  
Xing Song ◽  
Honglei Pei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colorectal Cancer ◽  
Pancreatic Cancer ◽  
Esophageal Cancer ◽  
Solid Tumors ◽  
Prognostic Value ◽  
Meta Analysis ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Background: It has been reported that miR-203 expression was aberrant in various types of cancers, and it could be used as a prognostic biomarker. Therefore, in this study, we aimed to evaluate the prognostic value of miR-203 expression in solid tumors by using meta-analysis and The Cancer Genome Atlas (TCGA) datasets. Methods: By doing a literature research in PubMed, Embase and the Cochrane Library (last update by December 2016), we were able to identify the studies assessing the prognostic role of miR-203 in various tumors. We then used TCGA datasets to validate the results of meta-analysis. Results:33 studies from 26 articles were qualified and enrolled in this meta-analysis. Pooled analyses showed that higher expression of miR-203 in tissues couldn’t predict poor overall survival (OS) and progression-free survival (PFS) in solid tumors. However, the results of subgroup analyses revealed that the upregulation of tissue miR-203 expression was associated with poor OS in colorectal cancer (hazard ratio (HR)=1.81, 95% confidence intervals (CI) 1.31-2.49; P<0.001), pancreatic cancer (HR=1.19, 95% CI 1.09-1.31; P<0.001) and ovarian cancer (HR=1.85, 95% CI 1.45-2.37; P<0.001); but it had opposite association in liver cancer (HR=0.52, 95% CI 0.28-0.97; P=0.040) and esophageal cancer (HR=0.41, 95% CI 0.25-0.66; P<0.001). Based on TCGA datasets, we found the same results for pancreatic cancer and esophageal cancer, but not for colorectal cancer and liver cancer. Moreover, patients with high circulating miR-203 in blood had significantly poor OS and PFS in colorectal cancer and breast cancer. Conclusion: Our study showed that the prognostic values of tissue miR-203 varied in different tumor types. In addition, the upregulation of circulating miR-203 in blood was associated with poor prognosis in colorectal cancer and breast cancer.

scholarly journals Screening and Identifying m6A Regulators as an Independent Prognostic Biomarker in Pancreatic Cancer Based on The Cancer Genome Atlas Database

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Bi Lin ◽  
Yangyang Pan ◽  
Dinglai Yu ◽  
Shengjie Dai ◽  
Hongwei Sun ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cox Regression ◽  
Malignant Tumors ◽  
Expression Profiles ◽  
Tumor Therapy ◽  
Disease Free Survival ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Background. Pancreatic cancer is one of the most malignant tumors of the digestive system, and its treatment has rarely progressed for the last two decades. Studies on m6A regulators for the past few years have seemingly provided a novel approach for malignant tumor therapy. m6A-related factors may be potential biomarkers and therapeutic targets. This research is focused on the gene characteristics and clinical values of m6A regulators in predicting prognosis in pancreatic cancer. Methods. In our study, we obtained gene expression profiles with copy number variation (CNV) data and clinical characteristic data of 186 patients with pancreatic cancer from The Cancer Genome Atlas (TCGA) portal. Then, we determined the alteration of m6a regulators and their correlation with clinicopathological features using the log-rank tests, Cox regression model, and chi-square test. Additionally, we validated the prognostic value of m6A regulators in the International Cancer Genome Consortium (ICGC). Results. The results suggested that pancreatic cancer patients with ALKBH5 CNV were associated with worse overall survival and disease-free survival than those with diploid genes. Additionally, upregulation of the writer gene ALKBH5 had a positive correlation with the activation of AKT pathways in the TCGA database. Conclusion. Our study not only demonstrated genetic characteristic changes of m6A-related genes in pancreatic cancer and found a strong relationship between the changes of ALKBH5 and poor prognosis but also provided a novel therapeutic target for pancreatic cancer therapy.

scholarly journals The Biological Function Delineated Across Pan-Cancer Levels Through lncRNA-Based Prognostic Risk Assessment Factors for Pancreatic Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Xudong Tang ◽  
Mengyan Zhang ◽  
Liang Sun ◽  
Fengyan Xu ◽  
Xin Peng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Prognostic Marker ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Research Network ◽  
Molecular Characteristics ◽  
Cancer Data ◽  
Cancer Genome Atlas ◽  
Pan Cancer ◽  
Genome Atlas

Long non-coding RNAs (lncRNAs) play key roles in tumors and function not only as important molecular markers for cancer prognosis, but also as molecular characteristics at the pan-cancer level. Because of the poor prognosis of pancreatic cancer, accurate assessment of prognosis is a key issue in the development of treatment plans for pancreatic cancer. Here we analyzed pancreatic cancer data from The Cancer Genome Atlas and The Genotype Tissue Expression database using Cox regression and lasso regression in analyses using a combination of the two databases as well as only The Cancer Genome Atlas database (Cancer Genome Atlas Research Network et al., 2013). A prognostic risk score model with significant correlation with pancreatic cancer survival was constructed, and two lncRNAs were investigated. Additional analysis of 33 cancers using the two lncRNAs showed that lncRNA TsPOAP1-AS1 was a prognostic marker of seven cancers, among which pancreatic cancer was the most significant, and lncRNA mi600hg was a prognostic marker of ovarian cancer and pancreatic cancer. LncRNA TsPOAP1-AS1 is associated with clinical stage and tumor mutation burden of some cancers as well as a strong degree of immune infiltration in many cancers, while a strong correlation between lncRNA mi600hg and microsatellite instability was observed in several cancers. The results of this study help further our understanding of the different functions of lncRNAs in cancer and may aid in the clinical application of lncRNAs as prognostic factors for cancer.

Dysregulated microRNAs in laryngeal cancer: a comprehensive meta-analysis using a robust rank aggregation approach

2020 ◽  
Vol 16 (33) ◽  
pp. 2723-2734
Author(s):  
Zaizai Cao ◽  
Yu Guo ◽  
Yinjie Ao ◽  
Shuihong Zhou
Keyword(s):  
Target Genes ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Meta Analysis ◽  
Enrichment Analysis ◽  
Rank Aggregation ◽  
The Cancer Genome Atlas ◽  
Aggregation Method ◽  
Multiple Cancer ◽  
Cancer Genome Atlas ◽  
Genome Atlas

We need a reasonable method of compiling data from different studies regarding the expression of microRNA (miRNA) in laryngeal squamous cell carcinoma (LSCC). The robust rank aggregation method was used to integrate the rank lists of miRNAs from 11 studies. The enrichment analysis was performed on target genes of meta-signature miRNAs. The Cancer Genome Atlas database was used to confirm the results of meta-analysis. Three meta-signature miRNAs (miR-21-5p, miR-196a-5p and miR-145-5p) were obtained. All three miRNAs could be prognostic for LSCC. The enrichment analysis showed that these miRNAs were associated significantly with multiple cancer-related signaling pathways. The robust rank aggregation approach is an effective way to identify important miRNAs from different studies. All identified miRNAs could be candidates for LSCC diagnostic and prognostic biomarkers.

scholarly journals Probe into the Target and Mechanism of Jianpi Xiaoke Prescription for Treating Type 2 Diabetes Mellitus through miRNA Expression Profiling

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Qiuyue Guo ◽  
Yunsheng Xu ◽  
Jie Li ◽  
Dan Luo ◽  
Jun Li ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Signaling Pathways ◽  
Mirna Expression ◽  
Expression Profiling ◽  
Target Genes ◽  
Cell Function ◽  
Control Group ◽  
Sequencing Data ◽  
Mirna Expression Profiling

Object. To probe into the target and molecular mechanism of Jianpi Xiaoke (JPXK) prescription in the treatment of type 2 diabetes through high-throughput microRNA (miRNA) sequencing. Methods. Ten of the 31 SPF male Wistar rats were randomly taken as the control group; the remaining rats were fed a high-sugar and high-fat diet, combined with Streptozotocin (STZ, 35 mg/kg) that induced a type 2 diabetes model. The model rats were randomly divided into model groups (n = 11) and the JPXK group (n = 10). After 8 weeks of JPXK intervention, we detected the function of islet cells through HE staining and ELISA. High-pass sequencing technology was adopted to identify the differential expression of miRNA to explore the target of JPXK treatment, assess the relevant target genes, conduct functional analysis, and lastly verify the sequencing data by qRT-PCR. Results. After treatment, FPG, FINS, and HOMA-IR levels of the treatment group improved significantly compared with those of the control group ( P < 0.05 ). Among the miRNAs differentially expressed between the model group and the control group, there were 7 reversals after JPXK treatment, including miR-1-3p, miR-135a-5p, miR-181d-5p, miR-206-3p, miR-215, miR-3473, and miR-547-3p (log2FC ≥ 1 or ≤ −1, P < 0.05 ). Besides, the 1810 target genes associated with these 7 miRNAs were assessed by multiMiR. According to the results of the GO and KEGG analyses, they were associated with biological processes (e.g., glucose transport and fat cell formation), and it covered multiple signaling pathways, capable of regulating islet cell function (e.g., MAPK, PI3K-Akt, Ras, AMPK, and HIF-1 signaling pathways). The PCR verification results were consistent with the sequencing results. Conclusion. This discovery interpreted the potential therapeutic targets and signaling pathways of JPXK prescription against T2DM based on miRNA expression profiling. In conclusion, our research provided novel research insights into traditional Chinese medicine (TCM) treatment of diabetes.

scholarly journals Serum microRNA Expression Profiling in Malaria Patients and Bioinformatic Analysis of Hsa-miR-106b-5p

2021 ◽  
Author(s):  
Jiacong Peng ◽  
Xiaohong Peng ◽  
Ying Wang ◽  
Liping Jiang ◽  
Dayu Li ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Mirna Expression ◽  
Expression Profiling ◽  
Target Genes ◽  
Small Gtpase ◽  
Differentially Expressed ◽  
Ppi Network ◽  
Kegg Analysis ◽  
Significant Difference ◽  
Mirna Expression Profiling

Abstract BackgroundMalaria, caused by Plasmodium, is one of the three major infectious diseases that se­riously endangers public health. Resistance to an­ti-malarial drugs and insecticides has made the prevention and control of malar­ia shown little improvement in the last four years. This study aimed to explore the changes in microRNA (miRNA) expression profiling of malaria patient and predict malaria-related miRNA by bioinformatics methods to provide theoretical basis for further verification of the correlation between specific miRNAs and immune regulation of malaria.MethodsSerum of patients infected by Plasmodium falciparum and healthy people from Myanmar border area was collected. miRNA expression profiling was obtained by RT-qPCR. Then the differentially expressed miRNA was screened and target genes were predicted by four miRNA databases (TargetScan, DIANA-microT, miRDB, and miRTarbase) and an intersection of target genes was obtained by Venn analysis. GO and KEGG analysis were performed for the overlapping target genes via Metascape. The results were further visualized by Cytoscape. Finally, Protein-protein interaction (PPI) network of predicted overlapping target genes was built by STRING.ResultsAmong the 341 tested serum miRNAs, 64 were differentially expressed in malaria patients (P<0.05), 27 miRNAs were up-regulated and 37 miRNAs were down-regulated. The miRNA with the most significant difference was hsa-miR-106b-5p (FC=14.871, adjusted.P.value<0.01); GO and KEGG analysis found that its overlapping predicted target gene set was remarkably enriched in biological functions such as GO:0007264~small GTPase mediated signal transduction, GO:0051056~regulation of small GTPase mediated signal transduction, GO:0051020~GTPase binding, GO:0048514~blood vessel morphogenesis(P<0.01) and signal pathway such as hsa04144: Endocytosis, hsa01521:EGFR tyrosine kinase inhibitor resistance, hsa05212:Pancreatic cancer (P<0.01); Besides, a PPI network containing 39 predicted target genes of hsa-miR-106b-5p was constructed, and 5 hub genes VEGFA, STAT3, RACGAP1, OCRL, and RBBP7 have been selected.ConclusionThe bioinformatics analysis results indicated that hsa-miR-106b-5p has a great relationship with malaria, it plays a part in inhibiting the emergence of ARTs resistance in Plasmodium and tumor progression, which may be achieved by regulating vascular morphogenesis, endocytosis, and VEGFA. The underlying mechanism needs to be further elucidated. We believe that this finding will facilitate an in-depth research on the as­sociation between malaria and miRNA.

scholarly journals The YAP1–NMU Axis Is Associated with Pancreatic Cancer Progression and Poor Outcome: Identification of a Novel Diagnostic Biomarker and Therapeutic Target

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1477 ◽  
Author(s):  
Yoo ◽  
Lee ◽  
Jun ◽  
Noh ◽  
Lee ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Epithelial Mesenchymal Transition ◽  
The Cancer Genome Atlas ◽  
Mesenchymal Transition ◽  
Tumor Group ◽  
Cancer Genome Atlas

Yes-associated protein (YAP)-1 is highly upregulated in pancreatic cancer and associated with tumor progression. However, little is known about the role of YAP1 and related genes in pancreatic cancer. Here, we identified target genes regulated by YAP1 and explored their role in pancreatic cancer progression and the related clinical implications. Analysis of different pancreatic cancer databases showed that Neuromedin U (NMU) expression was positively correlated with YAP1 expression in the tumor group. The Cancer Genome Atlas data indicated that high YAP1 and NMU expression levels were associated with poor mean and overall survival. YAP1 overexpression induced NMU expression and transcription and promoted cell motility in vitro and tumor metastasis in vivo via upregulation of epithelial–mesenchymal transition (EMT), whereas specific inhibition of NMU in cells stably expressing YAP1 had the opposite effect in vitro and in vivo. To define this functional association, we identified a transcriptional enhanced associate domain (TEAD) binding site in the NMU promoter and demonstrated that YAP1–TEAD binding upstream of the NMU gene regulated its transcription. These results indicate that the identified positive correlation between YAP1 and NMU is a potential novel drug target and biomarker in metastatic pancreatic cancer.

Genome-wide methylation and expression profiling identify methylation-associated genes in colorectal cancer

Epigenomics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 19-36 ◽  
Author(s):  
Xiaohui Sun ◽  
Diyu Chen ◽  
Ziqi Jin ◽  
Tianhui Chen ◽  
Aifen Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Expression Profiling ◽  
The Cancer Genome Atlas ◽  
Gene Overexpression ◽  
Normal Tissues ◽  
Atlas Data ◽  
Genome Wide ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Aim: To identify methylation-associated genes in the carcinogenesis of colorectal cancer (CRC). Materials & methods: Genome-wide patterns of DNA methylation and gene expression in CRC tissues and adjacent normal tissues were determined and further validated in The Cancer Genome Atlas data and Chinese CRC patients, respectively. Gene overexpression and knockdown cells were constructed to investigate their biological roles in CRC. Results: After validations, hypermethylation of eight genes were found to be correlated with their reduced transcription, and hypomethyaltion of three genes were associated with their upregulation. CADM3, CNRIP1, GRHL2, GRIA4, GSTM2 and NRXN1 were associated with the overall survival of CRC patients. CNRIP1 and GSTM2 were mainly responsible for the proliferation in CRC cells. Conclusion: A total of 11 genes may be promising biomarkers for CRC.

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