scholarly journals A Simple Nomogram Developed for Predicting HCC Metastasis Based on microRNAs

2021 ◽  
Author(s):  
Yong Zhu ◽  
Yusheng Jie ◽  
Yuankai Wu ◽  
Wenting Tang ◽  
Jing Cao ◽  
...  
Keyword(s):  
High Risk ◽  
Calibration Curve ◽  
Target Genes ◽  
Characteristic Curve ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Training Group ◽  
Gene Expression Omnibus ◽  
Functional Enrichment ◽  
Testing Group

Abstract Background: Owing to lack of predictive models for Hepatocellular carcinoma (HCC) metastasis based on the expression of miRNAs, we aimed to develop a simple model for identification of HCC patients at high risk of metastasis. Results: HCC datasets with metastasis information were acquired from the Gene Expression Omnibus (GEO), and samples were randomly divided into training group (n=169) and testing group (n=72). Based on expression of miRNAs in the training group, we developed a predictive nomogram for HCC metastasis and evaluated its performance using area under the receiver operating characteristic curve (AUC), calibration curve, decision curve and clinical impact curve analysis. We found that the expression of miR-30c, miR-185 and miR-323 in HCC correlated with metastasis by the least absolute shrinkage and selection operator regression (LASSO) method and multivariate logistic regression. Based on these three miRNAs, we generated the nomogram for predicting metastasis in the training group (AUC 0.869 [95% CI .813-0.925], sensitivity 80.5%, specificity 78.9%); in testing group (0.821 [0.770-0.872], 48.5%, 92.3%). The calibration curve showed a good agreement between actual observation and prediction by nomogram. The nomogram represented high clinical net benefits using decision curve. Moreover, total scores calculated by nomogram were higher in dead patients than that in alive patients. In addition, the predicted target genes of these 3 miRNAs correlated with tumor metastasis by functional enrichment analysis, such as filopodium and we identified their related hub genes. Conclusions: Our easy-to-use nomogram could assist in identifying HCC patients at high risk of metastasis, which offer valuable information for clinical treatment.

scholarly journals A Simple Nomogram Developed for Predicting HCC Metastasis Based on Micrornas 

2021 ◽  
Author(s):  
Yong Zhu ◽  
Yusheng Jie ◽  
Yuankai Wu ◽  
Wenting Tang ◽  
Jing Cao ◽  
...  
Keyword(s):  
High Risk ◽  
Calibration Curve ◽  
Target Genes ◽  
Characteristic Curve ◽  
Enrichment Analysis ◽  
Training Group ◽  
Clinical Impact ◽  
Curve Analysis ◽  
Functional Enrichment ◽  
Testing Group

Abstract BackgroundOwing to lack of predictive models for HCC metastasis based on the expression of miRNAs, we aimed to develop a simple model for identification of HCC patients at high risk of metastasis. MethodsHCC datasets with metastasis information were acquired from the Gene Expression Omnibus (GEO), and samples were randomly divided into training group (n=169) and testing group (n=72). Based on expression of miRNAs in the training group, we developed a predictive nomogram for HCC metastasis and evaluated its performance using area under the receiver operating characteristic curve (AUC), calibration curve, decision curve and clinical impact curve analysis.ResultsWe found that the expression of miR-30c, miR-185 and miR-323 in HCC correlated with metastasis by the least absolute shrinkage and selection operator regression (LASSO) method and multivariate logistic regression. Based on these three miRNAs, we generated the nomogram for predicting metastasis in the training group (AUC 0.869 [95% CI .813-0.925], sensitivity 80.5%, specificity 78.9%); in testing group (0.821 [0.770-0.872], 48.5%, 92.3%). The calibration curve showed a good agreement between actual observation and prediction by nomogram. The nomogram represented high clinical net benefits using decision curve and clinical impact curve analysis. Moreover, total scores calculated by nomogram were higher in dead patients than that in alive patients. In addition, the predicted target genes of these 3 miRNAs correlated with tumor metastasis by functional enrichment analysis, such as filopodium. Our easy-to-use nomogram could assist in identifying HCC patients at high risk of metastasis, which offer valuable information for clinical treatment.

scholarly journals Analysis of Serum miRNAs in Alzheimer’s Disease

2021 ◽  
Vol 36 ◽  
pp. 153331752110217
Author(s):  
Liu Lu ◽  
Wen-Zhuo Dai ◽  
Xi-Chen Zhu ◽  
Tao Ma
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Gene Interaction ◽  
Functional Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Mitogen Activated Protein Kinase ◽  
Regulatory Relationship

This paper was aimed to analyze the microRNA (miRNA) signatures in Alzheimer disease (AD) and find the significant expressions of miRNAs, their target genes, the functional enrichment analysis of the confirmed genes, and potential drug treatment. The miRNA expression information of the gene expression profile data was downloaded from the Gene Expression Omnibus database. The total data sample size is 1309, including 1021 AD samples and 288 normal samples. A total of 21 differentially expressed miRNAs were obtained, of which 16 (hsa-miR-6761-3p, hsa-miR-6747-3p, hsa-miR-6875-3p, hsa-miR-6754-3p, hsa-miR-6736-3p, hsa-miR-6762-3p, hsa-miR-6787-3p, hsa-miR-208a-5p, hsa-miR-6740-3p, hsa-miR-6778-3p, hsa-miR-595, hsa-miR-6753-3p, hsa-miR-4747-3p, hsa-miR-3646, hsa-miR-6716-3p and hsa-miR-4435) were up-regulated and 5 (hsa-miR-125a-3p, hsa-miR-22-3p, hsa-miR-24-3p, hsa-miR-6131 and hsa-miR-125b-1-3p) were down-regulated in AD. A total of 6 miRNAs (hsa-miR-595, hsa-miR-3646, hsa-miR-4435 hsa-miR-125a-3p, hsa-miR-22-3p and hsa-miR-24-3p) and 78 miRNA-disease-related gene sub-networks were predicted, and 116 ceRNA regulatory relationship pairs, and the ceRNA regulatory network were obtained. The results of enrichment analysis suggested that the main target pathways of several miRNAs differentially expressed in AD were mitogen-activated protein kinase signal pathway. According to the prediction results of Drug-Gene Interaction database 2.0, we obtained 53 pairs of drug-gene interaction, including 7 genes (PTGS2, EGFR, CALM1, PDE4D, FGFR2, HMGCR, cdk6) and 53 drugs. We hope our results are helpful to find a viable way to prevent, delay the onset, diagnose, and treat AD.

scholarly journals Integrative Bioinformatics Analysis Identifies Noninvasive miRNA Biomarkers for Lung Cancer

2021 ◽  
Author(s):  
Andrew Gao
Keyword(s):  
Lung Cancer ◽  
Messenger Rna ◽  
Target Genes ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Functional Enrichment ◽  
Nsclc Patients ◽  
Prognostic Power

AbstractNon-small cell lung cancer (NSCLC), a subtype of lung cancer, affects millions of people. While chemotherapy and other treatments have improved, the 5 year survival rate of NSCLC patients is still only 21%. Early diagnosis is essential for increasing survival as treatments have higher effectiveness at earlier stages of NSCLC. Noninvasive blood-based liquid biopsy tests for NSCLC may be useful for diagnosis and prognosis. MicroRNA (miRNA) and messenger RNA present in blood can serve as biomarkers for such tests. The present study identified 13 miRNAs that are underexpressed in the tissue and blood of NSCLC patients using Gene Expression Omnibus data. Following Kaplan Meier analysis, miR-140-3p, miR-29c, and miR-199a were selected as candidate biomarkers and demonstrated statistically significant prognostic power. An ROC analysis of miR-140-3p expression between NSCLC patients and controls had an area under curve value of 0.85. Functional enrichment analysis of the miRNA target genes revealed several overrepresented pathways relevant to cancer. Eight target genes were hub genes of the protein protein interaction network and possessed significant prognostic power. A combination of IL6, SNAI1, and CDK6 achieved a hazard ratio of 1.4 with p < 0.001. These biomarkers are especially valuable because they can be identified in blood and reflect the tumor state. Since all miRNAs were underexpressed in both tissue and blood, detecting expression of a biomarker miRNA in blood provides information on its expression in tissue as well. These miRNAs may be useful biomarkers for NSCLC prognostic and diagnostic tests and should be further studied.

scholarly journals Identification of Tumorigenic and Prognostic Biomarkers in Colorectal Cancer Based on microRNA Expression Profiles

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuntao Shi ◽  
Yingying Zhuang ◽  
Jialing Zhang ◽  
Mengxue Chen ◽  
Shangnong Wu
Keyword(s):  
Target Genes ◽  
Cox Regression ◽  
Expression Profiles ◽  
Survival Rates ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Risk Groups ◽  
Normal Mucosa ◽  
Microrna Expression ◽  
Functional Enrichment

Objective. Although noncoding RNAs, especially the microRNAs, have been found to play key roles in CRC development in intestinal tissue, the specific mechanism of these microRNAs has not been fully understood. Methods. GEO and TCGA database were used to explore the microRNA expression profiles of normal mucosa, adenoma, and carcinoma. And the differential expression genes were selected. Computationally, we built the SVM model and multivariable Cox regression model to evaluate the performance of tumorigenic microRNAs in discriminating the adenomas from normal tissues and risk prediction. Results. In this study, we identified 20 miRNA biomarkers dysregulated in the colon adenomas. The functional enrichment analysis showed that MAPK activity and MAPK cascade were highly enriched by these tumorigenic microRNAs. We also investigated the target genes of the tumorigenic microRNAs. Eleven genes, including PIGF, TPI1, KLF4, RARS, PCBP2, EIF5A, HK2, RAVER2, HMGN1, MAPK6, and NDUFA2, were identified to be frequently targeted by the tumorigenic microRNAs. The high AUC value and distinct overall survival rates between the two risk groups suggested that these tumorigenic microRNAs had the potential of diagnostic and prognostic value in CRC. Conclusions. The present study revealed possible mechanisms and pathways that may contribute to tumorigenesis of CRC, which could not only be used as CRC early detection biomarkers, but also be useful for tumorigenesis mechanism studies.

scholarly journals miRNA Mediated Noise Making of 3′UTR Mutations in Cancer

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 545 ◽  
Author(s):  
Wei Wu ◽  
Lingxiang Wu ◽  
Mengyan Zhu ◽  
Ziyu Wang ◽  
Min Wu ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
Target Genes ◽  
Expression Profiles ◽  
Tumor Development ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Messenger Rnas ◽  
Cellular Functions ◽  
Mrna Binding

Somatic mutations in 3′-untranslated regions (3′UTR) do not alter amino acids and are considered to be silent in cancers. We found that such mutations can promote tumor progression by altering microRNA (miRNA) targeting efficiency and consequently affecting miRNA–mRNA interactions. We identified 67,159 somatic mutations located in the 3′UTRs of messenger RNAs (mRNAs) which can alter miRNA–mRNA interactions (functional somatic mutations, funcMutations), and 69.3% of these funcMutations (the degree of energy change > 12 kcal/mol) were identified to significantly promote loss of miRNA-mRNA binding. By integrating mRNA expression profiles of 21 cancer types, we found that the expression of target genes was positively correlated with the loss of absolute affinity level and negatively correlated with the gain of absolute affinity level. Functional enrichment analysis revealed that genes carrying funcMutations were significantly enriched in the MAPK and WNT signaling pathways, and analysis of regulatory modules identified eighteen miRNA modules involved with similar cellular functions. Our findings elucidate a complex relationship between miRNA, mRNA, and mutations, and suggest that 3′UTR mutations may play an important role in tumor development.

scholarly journals 3131 ONCOSTREAMS: NOVEL DYNAMICS PATHOLOGICAL MULTICELLULAR STRUCTURES INVOLVED IN GLIOBLATOMA GROWTH AND INVASION

2019 ◽  
Vol 3 (s1) ◽  
pp. 111-111 ◽  
Author(s):  
Andrea Comba ◽  
Patrick Dunn ◽  
Anna E Argento ◽  
Padma Kadiyala ◽  
Sebastien Motsch ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Target Genes ◽  
Collective Motion ◽  
Malignant Tumors ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Genetically Engineered ◽  
Functional Enrichment ◽  
Low Grade ◽  
Normal Brain

OBJECTIVES/SPECIFIC AIMS: Oncostreams represent a novel growth pattern of GBM. In this study we uncovered the cellular and molecular mechanism that regulates the oncostreams function in GBM growth and invasion. METHODS/STUDY POPULATION: We studied oncostreams organization and function using genetically engineered mouse gliomas models (GEMM), mouse primary patient derived GBM model and human glioma biopsies. We evaluated the molecular landscape of oncostreams by laser capture microdissection (LCM) followed by RNA-Sequencing and bioinformatics analysis. RESULTS/ANTICIPATED RESULTS: Oncostreams are multicellular structures of 10-20 cells wide and 2-400 μm long. They are distributed throughout the tumors in mouse and human GBM. Oncostreams are heterogeneous structures positive for GFAP, Nestin, Olig2 and Iba1 cells and negative for Neurofilament. Using GEMM we found a negative correlation between oncostream density and animal survival. Moreover, examination of patient’s glioma biopsies evidenced that oncostreams are present in high grade but no in low grade gliomas. This suggests that oncostreams may play a role in tumor malignancy. Our data also indicated that oncostreams aid local invasion of normal brain. Transcriptome analysis of oncostreams revealed 43 differentially expressed (DE) genes. Functional enrichment analysis of DE genes showed that “collagen catabolic processes”, “positive regulation of cell migration”, and “extracellular matrix organization” were the most over-represented GO biological process. Network analysis indicated that Col1a1, ACTA2, MMP9 and MMP10 are primary target genes. These genes were also overexpressed in more malignant tumors (WT-IDH) compared to the less malignant (IDH1- R132H) tumors. Confocal time lapse imagining of 3D tumor slices demonstrated that oncostreams display a collective motion pattern within gliomas that has not been seen before. DISCUSSION/SIGNIFICANCE OF IMPACT: In summary, oncostreams are anatomically and molecularly distinctive, regulate glioma growth and invasion, display collective motion and are regulated by the extracellular matrix. We propose oncostreams as novel pathological markers valuable for diagnosis, prognosis and designing therapeutics for GBM patients.

scholarly journals Identification of Potential Biomarkers Associated with Basal Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yong Liu ◽  
Hui Liu ◽  
Queqiao Bian
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Characteristic Curve ◽  
External Validation ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Ppi Network ◽  
Microarray Datasets

Purpose. This work is aimed at identifying several molecular markers correlated with the diagnosis and development of basal cell carcinoma (BCC). Methods. The available microarray datasets for BCC were obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified between BCC and healthy controls. Afterward, the functional enrichment analysis and protein-protein interaction (PPI) network analysis of these screened DEGs were performed. An external validation for the DEG expression level was also carried out, and receiver operating characteristic curve analysis was used to evaluate the diagnostic values of DEGs. Result. In total, five microarray datasets for BCC were downloaded and 804 DEGs (414 upregulated and 390 downregulated genes) were identified. Functional enrichment analysis showed that these genes including CYFIP2, HOXB5, EGFR, FOXN3, PTPN3, CDC20, MARCKSL1, FAS, and PTCH1 were closely correlated with the cell process and PTCH1 played central roles in the BCC signaling pathway. Moreover, EGFR was a hub gene in the PPI network. The expression changes of six genes (CYFIP2, HOXB5, FOXN3, PTPN3, MARCKSL1, and FAS) were validated by an external GSE74858 dataset analysis. Finally, ROC analysis revealed that CYFIP2, HOXB5, PTPN3, MARCKSL1, PTCH1, and CDC20 could distinguish BCC and healthy individuals. Conclusion. Nine gene signatures (CYFIP2, HOXB5, EGFR, FOXN3, PTPN3, CDC20, MARCKSL1, FAS, and PTCH1) may serve as promising targets for BCC detection and development.

scholarly journals Downregulation of miRNA-205 Expression and Biological Mechanism in Prostate Cancer Tumorigenesis and Bone Metastasis

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Yu Sun ◽  
Sheng-Hua Li ◽  
Ji-Wen Cheng ◽  
Gang Chen ◽  
Zhi-Guang Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Protein Level ◽  
Target Genes ◽  
Mrna Level ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Forest Plot ◽  
Biological Mechanism

Background. The expression and mechanism of microRNA-205 (miRNA-205) in prostate cancer (PCa) and its bone metastasis remain controversial. Materials and Methods. The expression and discriminating capability of miRNA-205 were assessed by drawing a forest plot and a summarized receiver operating characteristic (SROC) curve, using data available from 27 miRNA-array and miRNA-sequencing datasets. The miRNA-205 target genes were acquired from online prediction tools, differentially upregulated genes in PCa, and differentially expressed genes (DEGs) after miRNA-205 transfection into PCa cell lines. Functional enrichment analysis was conducted to explore the biological mechanism of miRNA-205 targets. Immunohistochemistry (IHC) was applied to verify the protein level of the hub gene. Results. The expression of miRNA-205 in the PCa group (1,461 samples) was significantly lower than that in the noncancer group (510 samples), and the downregulation of miRNA-205 showed excellent sensitivity and specificity in differentiating between the two groups. In bone metastatic PCa, the miRNA-205 level was further reduced than in nonbone metastatic PCa, and it showed a good capability in distinguishing between the two groups. In total, 153 miRNA-205 targets were screened through the three aforementioned methods. Based on the results of functional enrichment analysis, the targets of miRNA-205 were mainly enriched during chromosome segregation and phospholipid-translocating ATPase activity and in the spindle microtubule and the p53 signaling pathway. CDK1 had the highest connectivity in the PPI network analysis and was screened as one of the hub genes. A statistically significant negative correlation between miRNA-205 and CDK1 was observed. The expression of CDK1 in PCa samples was pronouncedly upregulated in terms of both the mRNA level and the protein level when compared with noncancer samples. Conclusion. miRNA-205 may play a vital role in PCa tumorigenesis and bone metastasis by targeting CDK1.

scholarly journals System Analysis of MIRNAs in Maize Internode Elongation

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 417
Author(s):  
Chuanxi Peng ◽  
Xing Wang ◽  
Tianyu Feng ◽  
Rui He ◽  
Mingcai Zhang ◽  
...  
Keyword(s):  
Target Genes ◽  
System Analysis ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Internode Elongation ◽  
Differentially Expressed Mirnas ◽  
Post Transcriptional Regulation

MicroRNAs (miRNAs), the post-transcriptional gene regulators, are known to play an important role in plant development. The identification of differentially expressed miRNAs could better help us understand the post-transcriptional regulation that occurs during maize internode elongation. Accordingly, we compared the expression of MIRNAs between fixed internode and elongation internode samples and classified six differentially expressed MIRNAs as internode elongation-responsive miRNAs including zma-MIR160c, zma-MIR164b, zma-MIR164c, zma-MIR168a, zma-MIR396f, and zma-MIR398b, which target mRNAs supported by transcriptome sequencing. Functional enrichment analysis for predictive target genes showed that these miRNAs were involved in the development of internode elongation by regulating the genes respond to hormone signaling. To further reveal how miRNA affects internode elongation by affecting target genes, the miRNA–mRNA–PPI (protein and protein interaction) network was constructed to summarize the interaction of miRNAs and these target genes. Our results indicate that miRNAs regulate internode elongation in maize by targeting genes related to cell expansion, cell wall synthesis, transcription, and regulatory factors.

scholarly journals Differential co-expression network analysis for identification of functional modules in HIV infection and tubercolosis-HIV co-infection

2016 ◽  
Vol 89 (2) ◽  
Author(s):  
Mohit Jha ◽  
Anvita Gupta ◽  
Sudha Singh ◽  
Khushhali Menaria Pandey
Keyword(s):  
Network Analysis ◽  
Hiv Infection ◽  
Enrichment Analysis ◽  
Gene Interaction ◽  
Gene Clusters ◽  
Functional Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Functional Enrichment ◽  
Specific Gene ◽  
Diagnostic Strategies

Co-infection with tuberculosis (TB) is the preeminent cause of demise in human immunodeficiency virus (HIV) infected individuals. However, diagnosis of TB, particularly in the presence of an HIV co-infection, can be limiting owing to the high inaccuracy associated with conventional diagnostic strategies. Here we determine dysregulated pathways in TB-HIV co-infection and HIV infection utilizing coexpression networks. Primarily, we utilized preservation statistics to identify gene modules that exhibit a weak conservation of network topology within HIV infected and TB-HIV co-infected networks. Raw data was downloaded from Gene Expression Omnibus (GSE50834) and duly pre-processed. Co-expression networks for each condition (HIV infected and TB-HIV co-infected) were constructed independently. Preservation of HIV infected network edges was evaluated with respect to TB-HIV co-infected and vice versa using weighted correlation network analysis. Two out of the 22 modules were identified as exhibiting weak preservation in both conditions. Functional enrichment analysis identified that weakly preserved modules were pertinent to the condition under study. For instance, weakly preserved TBHIV co-infected module T1 enriched for genes associated with mitochondrion exhibited the highest fraction of gene interaction pairs exclusive to TB-HIV co-infection. Concisely, we illustrated the application of using preservation statistics to detect modules functionally linked with dysregulated pathways in disease, as exemplified by the mitochondrion module T1. Our analyses discovered gene clusters that are non-randomly linked with the disease. Highly specific gene pairs pointed to interactions between known markers of disease and favoured identification of possible markers that are likely to be associated with the disease.

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