scholarly journals Identification of prognostic factors for intrahepatic cholangiocarcinoma using long non-coding RNAs-associated ceRNA network

2020 ◽  
Author(s):  
Zhichen Kang ◽  
Lixin Guo ◽  
Zhuo Zhu ◽  
Rongfeng Qu
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Signaling Pathway ◽  
Intrahepatic Cholangiocarcinoma ◽  
Messenger Rna ◽  
Transcriptome Sequencing ◽  
Pathway Enrichment Analysis ◽  
Sequencing Data ◽  
Cerna Network ◽  
Non Coding Rnas

Abstract Background: Accumulating amount of evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor pathogenesis. However, the roles of long non coding RNAs (lncRNAs) in the lncRNA-related ceRNA network of intrahepatic cholangiocarcinoma (ICC) still remain enigmatic. The current study aims to identify prognostic factors in the lncRNA-related ceRNA network of ICC.Methods: The transcriptome sequencing data of lncRNAs, messenger RNA (mRNA) and microRNA (miR) were downloaded from the SRA and TCGA databases. Differentially expressed lncRNAs (DElncRNAs), DEmiRs and DEmRNAs were identified and adopted to construct an lncRNA-miR-mRNA ceRNA network. ICC-associated DEmRNAs were adopted to construct the protein-protein interaction (PPI) network. The expression of the top 6 genes in the hub module was validated with mRNA transcriptome sequencing data and ICC-related gene expression dataset GSE45001, followed by GO and KEGG pathway enrichment analysis. The relationship between the hub gene-associated ceRNA network and the overall survival of patients with ICC was predicted by conducting a Kaplan-Meier survival analysis. Results: Sixty co-expressed DEmRNAs were identified in the ceRNA network. The top 6 hub genes consisted of downregulated FOS, IGF2, FOXO1 and NTF3, upregulated IGF1R, and insignificantly downregulated HGF in ICC tissues, when compared to that of normal adjacent tissues, followed by the successful construction of lncRNA-miR-hub network consisting of 86 ceRNA modules. MME-AS1 and hsa-miR-182 were associated with overall survival in ICC patients. FOS, IGF1R, IGF2, FOXO1, and NTF3 might target “TGF-β signaling pathway”, “the hedgehog signaling pathway”, “retinol metabolism”, or “type II diabetes mellitus” pathways respectively. Conclusion: These results indicate that FOS, IGF1R, IGF2, FOXO1, and NTF3 were useful prognostic factors in determining the prognosis of patients with ICC.

scholarly journals Identification of prognostic factors for intrahepatic cholangiocarcinoma based on long non-coding RNAs-associated ceRNA network

2020 ◽  
Author(s):  
Zhichen Kang ◽  
Lixin Guo ◽  
Zhuo Zhu ◽  
Rongfeng Qu
Keyword(s):  
Prognostic Factors ◽  
Intrahepatic Cholangiocarcinoma ◽  
Messenger Rna ◽  
Transcriptome Sequencing ◽  
Tumor Biology ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Sequencing Data ◽  
Cerna Network ◽  
Non Coding Rnas

Abstract Background Accumulating evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor biology. However, the roles of cancer long non coding RNAs (lncRNAs) in lncRNA-related ceRNA network of intrahepatic cholangiocarcinoma (ICC) remain enigmatic. The current study aims to identify prognostic factors in the lncRNA-related ceRNA network of ICC. Methods The transcriptome sequencing data of the lncRNAs, messenger RNA (mRNA) and microRNA (miR) were downloaded from SRA, and TCGA database respectively. Differentially expressed lncRNAs (DElncRNAs), DEmiRs and DEmRNAs were identified and adopted to construct lncRNA-miR-mRNA ceRNA network. ICC-associated DEmRNAs were adopted to construct the PPI network. The expression of the top 6 genes in the hub module was validated in mRNA transcriptome sequencing data and ICC-related gene expression dataset GSE45001, followed by GO and KEGG pathway enrichment analysis. The potential function of genes in hub module in the ceRNA network was finally subjected to GSEA. Results Sixty coexpression DEmRNAs were identified in the ceRNA network. The 6 top genes in the hub module consists of FOS, HGF, IGF2, FOXO1, NTF3 (downregulated), and IGF1R (upregulated) in ICC tissues compared to normal adjacent tissues, followed by the successful construction of lncRNA-miR-hub network with 86 ceRNA modules. FOS, IGF2 or IGF1R might regulate the development of ICC by targeting “N-glycan biosynthesis”, “α-linolenic acid metabolism” or “type II diabetes” pathways respectively. Conclusion These results show FOS, IGF2 and IGF1R serve as prognostic factors of ICC patients.

scholarly journals Integrative Analysis of lncRNAs, miRNAs, and mRNA-Associated ceRNA Network in an Atopic Dermatitis Recurrence Model

2018 ◽  
Vol 19 (10) ◽  
pp. 3263 ◽  
Author(s):  
Xiaoyu Wang ◽  
Kaifan Bao ◽  
Peng Wu ◽  
Xi Yu ◽  
Can Wang ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Messenger Rna ◽  
Integrative Analysis ◽  
Ample Evidence ◽  
Cerna Network ◽  
Non Coding Rna ◽  
Recurrence Model ◽  
Non Coding Rnas ◽  
Remission Phase ◽  
Long Non Coding Rna

Atopic dermatitis (AD) is a prevalent inflammatory skin disease characterized by its chronic nature and relapse. Ample evidence suggests that non-coding RNAs play a major role in AD pathogenesis. However, the mechanism remains unknown, particularly in AD recurrence. Dynamic morphological and cytokine changes were measured throughout the whole course of an FITC-induced AD recurrence murine model. Microarray assay and integrative analysis were performed to comprehensively explore long non-coding RNA (lncRNA), messenger RNA (mRNA), and microRNA (miRNA) networks. Our results showed that an AD recurrence model was established. Overall, 5766 lncRNAs, 4025 mRNAs, and 202 miRNAs changed after elicitation, whereas, 419 lncRNAs, 349 mRNAs, and more notably, only 23 miRNAs, were dysregulated in the remission phase. Gene ontology (GO) and KEGG pathway enrichment analyses were used to investigate the potential functions of the dysregulated genes. The altered regulation of seven miRNAs and seven lncRNAs were validated in different stages of the model. The competing endogenous RNA (ceRNA) network inferred that lncRNA humanlincRNA0490+ could compete for miR-155-5p binding, through which it might affect Pkiα expression. Altogether, our findings have provided a novel perspective on the potential roles of non-coding RNAs in AD, and suggest that specific non-coding RNAs could be new therapeutic targets against AD recurrence.

scholarly journals Prognostic Factors for Overall Survival in Advanced Intrahepatic Cholangiocarcinoma Treated with Yttrium-90 Radioembolization

2019 ◽  
Vol 9 (1) ◽  
pp. 56 ◽  
Author(s):  
Michael Köhler ◽  
Fabian Harders ◽  
Fabian Lohöfer ◽  
Philipp M. Paprottka ◽  
Benedikt M. Schaarschmidt ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Liver Disease ◽  
Surgical Resection ◽  
Intrahepatic Cholangiocarcinoma ◽  
Tumor Volume ◽  
Cox Regression ◽  
Tertiary Care ◽  
Liver Volume ◽  
Total Liver Volume

Purpose: To evaluate factors associated with survival following transarterial 90Y (yttrium) radioembolization (TARE) in patients with advanced intrahepatic cholangiocarcinoma (ICC). Methods: This retrospective multicenter study analyzed the outcome of three tertiary care cancer centers in patients with advanced ICC following resin microsphere TARE. Patients were included either after failed previous anticancer therapy, including relapse after surgical resection, or for having a minimum of 25% of total liver volume affected by ICC. Patients were stratified and response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at 3 months. Kaplan–Meier analysis was performed to analyze survival followed by cox regression to determine independent prognostic factors for survival. Results: 46 patients were included (19 male, 27 female), median age 62.5 years (range 29–88 years). A total of 65% of patients had undergone previous therapy, while 63% had a tumor volume > 25% of the entire liver volume. Median survival was 9.5 months (95% CI: 6.1–12.9 months). Due to loss in follow-up, n = 37 patients were included in the survival analysis. Cox regression revealed the extent of liver disease to one or both liver lobes being associated with survival, irrespective of tumor volume (p = 0.041). Patients with previous surgical resection of ICC had significantly decreased survival (3.9 vs. 12.8 months, p = 0.002). No case of radiation-induced liver disease was observed. Discussion: Survival after 90Y TARE in patients with advanced ICC primarily depends on disease extent. Only limited prognostic factors are associated with a general poor overall survival.

scholarly journals Comprehensive circRNA Expression Profile and Construction of circRNAs-Related ceRNA Network in a Mouse Model of Autism

2021 ◽  
Vol 11 ◽  
Author(s):  
Ji Wang ◽  
Zhongxiu Yang ◽  
Canming Chen ◽  
Yang Xu ◽  
Hongguang Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Expression Profile ◽  
Enrichment Analysis ◽  
Notch Signaling Pathway ◽  
Mapk Signaling ◽  
Circular Rnas ◽  
Pathway Enrichment Analysis ◽  
Common Disease ◽  
Cerna Network

Autism is a common disease that seriously affects the quality of life. The role of circular RNAs (circRNAs) in autism remains largely unexplored. We aimed to detect the circRNA expression profile and construct a circRNA-based competing endogenous RNA (ceRNA) network in autism. Valproate acid was used to establish an in vivo model of autism in mice. A total of 1,059 differentially expressed circRNAs (477 upregulated and 582 downregulated) in autism group was identified by RNA sequencing. The expression of novel_circ_015779 and novel_circ_035247 were detected by real-time PCR. A ceRNA network based on altered circRNAs was established, with 9,715 nodes and 150,408 edges. Module analysis was conducted followed by GO and KEGG pathway enrichment analysis. The top three modules were all correlated with autism-related pathways involving “TGF-beta signaling pathway,” “Notch signaling pathway,” “MAPK signaling pathway,” “long term depression,” “thyroid hormone signaling pathway,” etc. The present study reveals a novel circRNA involved mechanisms in the pathogenesis of autism.

scholarly journals A Pan-Cancer Analysis of Alternative Splicing Events Reveals Novel Tumor-Associated Splice Variants of Matriptase

2014 ◽  
Vol 13 ◽  
pp. CIN.S19435 ◽  
Author(s):  
Daryanaz Dargahi ◽  
Richard D. Swayze ◽  
Leanna Yee ◽  
Peter J. Bergqvist ◽  
Bradley J. Hedberg ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
High Throughput ◽  
Messenger Rna ◽  
Transcriptome Sequencing ◽  
Splice Variants ◽  
Flow Cytometric Analysis ◽  
Chinese Hamster ◽  
Lung Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Sequencing Data

High-throughput transcriptome sequencing allows identification of cancer-related changes that occur at the stages of transcription, pre-messenger RNA (mRNA), and splicing. In the current study, we devised a pipeline to predict novel alternative splicing (AS) variants from high-throughput transcriptome sequencing data and applied it to large sets of tumor transcriptomes from The Cancer Genome Atlas (TCGA). We identified two novel tumor-associated splice variants of matriptase, a known cancer-associated gene, in the transcriptome data from epithelial-derived tumors but not normal tissue. Most notably, these variants were found in 69% of lung squamous cell carcinoma (LUSC) samples studied. We confirmed the expression of matriptase AS transcripts using quantitative reverse transcription PCR (qRT-PCR) in an orthogonal panel of tumor tissues and cell lines. Furthermore, flow cytometric analysis confirmed surface expression of matriptase splice variants in chinese hamster ovary (CHO) cells transiently transfected with cDNA encoding the novel transcripts. Our findings further implicate matriptase in contributing to oncogenic processes and suggest potential novel therapeutic uses for matriptase splice variants.

scholarly journals Mechanistic Insight Into the Regulation of Immune-Related Genes Expression in Autism Spectrum Disorder

2021 ◽  
Vol 8 ◽  
Author(s):  
Hani Sabaie ◽  
Hossein Dehghani ◽  
Shadi Shiva ◽  
Mohammad Reza Asadi ◽  
Omidvar Rezaei ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Pathway Enrichment Analysis ◽  
Cerna Network ◽  
Immune Related Genes ◽  
Rna Interaction

Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder featuring impairment in verbal and non-verbal interactions, defects in social interactions, stereotypic behaviors as well as restricted interests. In recent times, the incidence of ASD is growing at a rapid pace. In spite of great endeavors devoted to explaining ASD pathophysiology, its precise etiology remains unresolved. ASD pathogenesis is related to different phenomena associated with the immune system; however, the mechanisms behind these immune phenomena as well as the potential contributing genes remain unclear. In the current work, we used a bioinformatics approach to describe the role of long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) in the peripheral blood (PB) samples to figure out the molecular regulatory procedures involved in ASD better. The Gene Expression Omnibus database was used to obtain the PB microarray dataset (GSE89594) from the subjects suffering from ASD and control subjects, containing the data related to both mRNAs and lncRNAs. The list of immune-related genes was obtained from the ImmPort database. In order to determine the immune-related differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs), the limma package of R software was used. A protein-protein interaction network was developed for the immune-related DEmRNAs. By employing the Human MicroRNA Disease Database, DIANA-LncBase, and DIANA-TarBase databases, the RNA interaction pairs were determined. We used the Pearson correlation coefficient to discover the positive correlations between DElncRNAs and DEmRNAs within the ceRNA network. Finally, the lncRNA-associated ceRNA network was created based on DElncRNA-miRNA-DEmRNA interactions and co-expression interactions. In addition, the KEGG enrichment analysis was conducted for immune-related DEmRNAs found within the constructed network. This work found four potential DElncRNA-miRNA-DEmRNA axes in ASD pathogenesis, including, LINC00472/hsa-miR-221-3p/PTPN11, ANP32A-IT1/hsa-miR-182-5p/S100A2, LINC00472/hsa-miR-132-3p/S100A2, and RBM26-AS1/hsa-miR-182-5p/S100A2. According to pathway enrichment analysis, the immune-related DEmRNAs were enriched in the “JAK-STAT signaling pathway” and “Adipocytokine signaling pathway.” An understanding of regulatory mechanisms of ASD-related immune genes would provide novel insights into the molecular mechanisms behind ASD pathogenesis.

scholarly journals Systematic Transcriptome Analysis Reveals the Inhibitory Function of Cinnamaldehyde in Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Ru Chen ◽  
Juan Wu ◽  
Chang Lu ◽  
Ting Yan ◽  
Yu Qian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Transcriptome Sequencing ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cerna Network ◽  
Whole Transcriptome Sequencing ◽  
Whole Transcriptome

Cinnamaldehyde (CA) is the main component extracted from the traditional Chinese medicine cinnamon. Recent studies revealed that CA has antiviral and anti-tumor effects. However, the effect and mechanism of CA on non-small cell lung cancer (NSCLC) through whole transcriptome sequencing integrated analysis have not been systematically investigated. In this study, whole transcriptome sequencing was used to identify differentially expressed messenger RNAs (mRNAs), micro RNAs (miRNAs), and long non-coding RNAs (lncRNAs) that were influenced by CA and screen regulatory pathways. The results showed that CA significantly inhibited proliferation, invasion, and migration, whereas it induced the apoptosis of NSCLC cells. CA inhibited tumor growth in vivo. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that these differentially expressed mRNAs were potentially implicated in the CA-suppressing malignant phenotypes of NSCLC. According to the competing endogenous RNA (ceRNA) hypothesis, a ceRNA network was constructed, including 13 mRNAs, 6 miRNAs, and 11 lncRNAs. Kyoto Encyclopedia of Genes and Genomes analysis of the 13 mRNAs in the ceRNA network showed that suppressors of cytokine signaling 1 (SOCS1), BTG anti-proliferation factor 2 (BTG2), and Bruton tyrosine kinase (BTK) were significantly enriched in the JAK/STAT signaling pathway, RNA degradation, and nuclear factor-κB (NF-κB) signaling pathway related to cancer. These findings indicated that SOCS1, BTG2, and BTK play an essential role in CA against NSCLC. Meanwhile, based on the ceRNA network, three lncRNAs (long intergenic non-protein coding RNA 1504 [LINC01504], LINC01783, and THUMPD3 antisense RNA 1 [THUMPD3-AS1]) and three miRNAs (has-miR-155-5p, has-miR-7-5p, and has-miR-425-5p) associated with SOCS1, BTG2, and BTK may be important in CA against NSCLC. Taken together, the present study demonstrated the activity of CA against lung cancer and its potential use as a therapeutic agent.

scholarly journals Nomograms predict survival outcome of Klatskin tumors patients

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8570
Author(s):  
Feng Qi ◽  
Bin Zhou ◽  
Jinglin Xia
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Lymph Node ◽  
Intrahepatic Cholangiocarcinoma ◽  
Poor Prognosis ◽  
Survival Rates ◽  
Klatskin Tumor ◽  
Tumor Patients ◽  
Klatskin Tumors

Objective Klatskin tumors are rare, malignant tumors of the biliary system with a poor prognosis for patient survival. The current understanding of these tumors is limited to a small number of case reports or case series; therefore, we examined prognostic factors of this disease. Methods A population cohort study was conducted in patients selected from the Surveillance, Epidemiology, and End Results (SEER) database with a Klatskin tumor that was histologically diagnosed between 2004 to 2014. Propensity-matching (PSM) analysis was performed to determine the overall survival (OS) among those with a Klatskin tumor (KCC), intrahepatic cholangiocarcinoma (ICCA), or hepatocellular carcinoma (HCC). The nomogram was based on 317 eligible Klatskin tumor patients and its predictive accuracy and discriminatory ability were determined using the concordance index (C-index). Results Kaplan-Meier analysis showed that patients with Klatskin tumors had significantly worse overall survival rates (1-year OS = 26.2%, 2-year OS = 10.7%, 3-year OS = 3.4%) than those with intrahepatic cholangiocarcinoma (1-year OS = 62.2%, 2-year OS = 36.4%, 3-year OS = 19.1%, p < 0.001) or hepatocellular carcinoma (1-year OS = 72.4% , 2-year OS = 48.5%, 3-year OS = 36.2%, p < 0.001). A poor prognosis was also significantly associated with older age, higher grade, SEER historic stage, and lymph node metastasis. Local destruction of the tumor (HR = 0.635, 95% CI [0.421–0.956], p = 0.03) and surgery (HR = 0.434, 95% [CI 0.328–0.574], p < 0.001) were independent protective factors. Multivariate Cox analysis showed that older age, SEER historic stage, and lymph node metastases (HR = 1.468, 95% CI [1.008–2.139], p = 0.046) were independent prognostic factors of poor survival rates in Klatskin tumor patients, while cancer-directed surgery was an independent protective factor (HR = 0.555, 95% CI [0.316–0.977], p = 0.041). The prognostic and protective factors were included in the nomogram (C-index for survival = 0.651; 95% CI [0.607–0.695]). Conclusions The Klatskin tumor group had poorer rates of OS and cancer-specific survival than the ICCA and HCC groups. Early detection and diagnosis were associated with a higher rate of OS in Klatskin tumor patients.

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