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

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.

2018 ◽  
Vol 46 (3) ◽  
pp. 925-952 ◽  
Author(s):  
Rong-quan He ◽  
Wei-luan Cen ◽  
Jie-mei Cen ◽  
Wei-ning Cen ◽  
Jia-yi Li ◽  
...  

Background/Aims: Since the function of microRNA (miR)-210 in non-small cell lung cancer (NSCLC) remains unclear, we aimed to explore the clinical significance of miR-210 in NSCLC. Methods: NSCLC-related data from 1673 samples on Gene Expression Omnibus and 1090 samples on The Cancer Genome Atlas were obtained and analyzed. The expression level of miR-210 was validated via real-time quantitative PCR analysis with 125 paired clinical samples. A meta-analysis was performed to generate a comprehensive understanding of miR-210 expression and its clinical significance in NSCLC. In addition, bioinformatics analysis was also conducted to reveal the potential underlying mechanism of miR-210 action in NSCLC. Results: miR-210 expression was consistently elevated in NSCLC solid tissue samples. However, its expression was controversial in easily obtained body fluids (i.e., blood, plasma, and serum). Moreover, an overall pooled meta-analysis implied a comparatively higher level of miR-210 expression in NSCLC cancerous tissue than in normal control tissue (P < 0.001). In addition, a meta-analysis of outcome revealed a significant diagnostic capacity of miR-210 in NSCLC by detecting its expression in serum and sputum (area under the summary receiver operating characteristic curve 0.82 and 0.81, respectively). miR-210 overexpression was associated with poor progression-free survival (PFS) in NSCLC and was negatively related to overall survival and disease-free survival. Bioinformatic gene enrichment and annotation analyses showed that the target genes of miR-210 were greatly enriched in cell adhesion and plasma membrane, and three pathways were considered to be the main functional circuits of miR-210: renin secretion, the cGMP-PKG signaling pathway, and cell adhesion molecules. Conclusion: In NSCLC, miR-210 expression was elevated and overexpression indicated poor PFS. Expression level of miR-210 in serum and sputum showed significant diagnostic value for NSCLC.


2017 ◽  
Vol 41 (4) ◽  
pp. 1468-1480 ◽  
Author(s):  
Yingjie Shao ◽  
Wendong Gu ◽  
Zhonghua Ning ◽  
Xing Song ◽  
Honglei Pei ◽  
...  

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.


Epigenomics ◽  
2021 ◽  
Author(s):  
Haoya Xu ◽  
Xianli Li ◽  
Shengtan Wang ◽  
Feifei Li ◽  
Jian Gao ◽  
...  

Aims: To explore the pathways and target genes related to N6-methyladenosine (m6A) methylation in ovarian cancer and their effect on patient prognosis. Methods & materials: The Cancer Genome Atlas was used to screen genes related to m6A regulators in terms of gene expression, mutation and copy number variation. These genes were subjected to pathway enrichment analysis. Prognosis-related genes were screened and involved in risk signature construction. Immunohistochemistry was used for verification. Results: We obtained 1408 genes dysregulated in parallel to m6A regulators, which were mainly involved in the platelet activation pathway. The m6A-related signature was constructed based on the expression of four prognosis-related genes ( RPS6KA2, JUNB, HNF4A and P2RX1). Conclusion: This work provides new insights into the mechanism of m6A methylation in ovarian cancer.


2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Elif Pala ◽  
Tuba Denkçeken

AbstractMicroRNAs (miRNAs) have been proven to play a crucial role in postmenopausal osteoporosis (PMO), and studies on their diagnostic value have been increasing. In our study, we aim to identify the key miRNAs in the PMO that might be potential biomarkers. A comprehensive systematic literature search was conducted by searching PubMed, Web of Science, Embase and Cochrane Library databases. In the total of 16 independent miRNA expression studies which contained 327 PMO patients and 328 postmenopausal (PM) healthy control samples, miRNAs were evaluated by using robust rank aggregation (RRA) method. A statistically significant meta-signature of up-regulated hsa-miR-133a-3p (P = 1.38e−03) was determined. Then bioinformatics analysis to recruit putative target genes prediction of hsa-miR-133a-3p and pathway enrichment analysis to reveal what biological processes this miRNA may affect were conducted. It was indicated that pathways were commonly associated with adrenergic signaling in cardiomyocytes, adherens junction, PI3K-Akt signaling pathway and AMPK signaling pathway. Furthermore, STRING and Cytoscape tools were used to visualize the interactions between target genes of hsa-miR-133a-3p. Six genes were detected as hub genes among 576 targets which were CDC42, RHOA, EGFR, VAMP2, PIK3R2 and FN1. After Kyoto Encyclopedia of Genes and Genomes pathway analysis, it was detected that these hub genes were mostly enriched in signaling pathways and cancer. In this meta-analysis, it is stated that circulating hsa-miR-133a-3p may serve as a potential non-invasive biomarker and therapeutic target in PMO.


2018 ◽  
Vol 49 (2) ◽  
pp. 678-695 ◽  
Author(s):  
Zhigang Zhang ◽  
Bing Pan ◽  
Shaocheng Lv ◽  
Zhiwei Ji ◽  
Qian Wu ◽  
...  

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.


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3089 ◽  
Author(s):  
Hong Yang ◽  
Xin Zhang ◽  
Xiao-yong Cai ◽  
Dong-yue Wen ◽  
Zhi-hua Ye ◽  
...  

BackgroundLiver hepatocellular carcinoma accounts for the overwhelming majority of primary liver cancers and its belated diagnosis and poor prognosis call for novel biomarkers to be discovered, which, in the era of big data, innovative bioinformatics and computational techniques can prove to be highly helpful in.MethodsBig data aggregated from The Cancer Genome Atlas and Natural Language Processing were integrated to generate differentially expressed genes. Relevant signaling pathways of differentially expressed genes went through Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes and Panther pathway enrichment analysis and protein-protein interaction network. The pathway ranked high in the enrichment analysis was further investigated, and selected genes with top priority were evaluated and assessed in terms of their diagnostic and prognostic values.ResultsA list of 389 genes was generated by overlapping genes from The Cancer Genome Atlas and Natural Language Processing. Three pathways demonstrated top priorities, and the one with specific associations with cancers, ‘pathways in cancer,’ was analyzed with its four highlighted genes, namely, BIRC5, E2F1, CCNE1, and CDKN2A, which were validated using Oncomine. The detection pool composed of the four genes presented satisfactory diagnostic power with an outstanding integrated AUC of 0.990 (95% CI [0.982–0.998],P < 0.001, sensitivity: 96.0%, specificity: 96.5%). BIRC5 (P = 0.021) and CCNE1 (P = 0.027) were associated with poor prognosis, while CDKN2A (P = 0.066) and E2F1 (P = 0.088) demonstrated no statistically significant differences.DiscussionThe study illustrates liver hepatocellular carcinoma gene signatures, related pathways and networks from the perspective of big data, featuring the cancer-specific pathway with priority, ‘pathways in cancer.’ The detection pool of the four highlighted genes, namely BIRC5, E2F1, CCNE1 and CDKN2A, should be further investigated given its high evidence level of diagnosis, whereas the prognostic powers of BIRC5 and CCNE1 are equally attractive and worthy of attention.


2020 ◽  
Vol 10 (8) ◽  
pp. 1189-1196
Author(s):  
Kaikai Ren ◽  
Jiakang Ma ◽  
Bo Zhou ◽  
Xiaoyan Lin ◽  
Mingyu Hou ◽  
...  

Hepatocellular carcinoma (HCC) is a malignancy originating from hepatocytes with a high rate of distant metastasis and recurrence. HCC prognosis remains poorly understood, although its diagnosis and treatment have improved globally. Therefore, it is necessary to identify reliable predictive and prognostic indicators of HCC. HCC gene expression profiles and corresponding clinical data were downloaded from The Cancer Genome Atlas. Seven lncRNAs (C10orf91, AC011352.3, AC015722.2, AC006372.1, PICSAR, AC110285.3, and AP001972.4) associated with immune and clinicopathological features were identified as biomarker candidates for HCC prognosis based on single-sample gene set enrichment analysis, the ESTIMATE algorithm, and Cox PHR analyses. Altogether, the findings revealed that the seven immune-related lncRNAs may provide a reference for improving HCC prognosis.


2021 ◽  
Author(s):  
Jialin Li ◽  
Xinliang Gao ◽  
Suyan Tian ◽  
Mingbo Tang ◽  
Wei Liu

Background: Exosomes are involved in tumorigenesis, growth and metastasis. However, the prognostic value of exosome-related genes in lung adenocarcinoma (LUAD) remains unclear. Methods: Clinical and transcriptome data from The Cancer Genome Atlas LUAD cohort were used to construct a model based on exosome-related genes, which was validated with LUAD data from the Gene Expression Omnibus (GEO). Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were used to explore underlying mechanisms; the single-sample gene set enrichment analysis score was used to determine immune functions. Results: A 19-exosome-related gene signature for overall survival in LUAD was predictive in both The Cancer Genome Atlas and GEO LUAD cohorts. Immune-related and extracellular matrix-related pathways were enriched in differentially expressed genes. Immune states differed between high- and low-risk groups. Conclusion: The novel signature can be used to predict outcomes in LUAD.


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