scholarly journals Identifying Differentially Expressed MicroRNAs Between Cirrhotic and Non-Cirrhotic Hepatocellular Carcinoma and Exploring Their Functions Using Bioinformatic Analysis

2018 ◽  
Vol 48 (4) ◽  
pp. 1443-1456 ◽  
Author(s):  
Ying Mei ◽  
Yu You ◽  
Jin Xia ◽  
Jian-Ping Gong ◽  
Yun-Bing Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Bioinformatic Analysis ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Online Tools ◽  
Tumor Stages ◽  
Differentially Expressed Mirnas ◽  
Cancer Genome Atlas ◽  
Cirrhotic Patients ◽  
Independent Risk Factors

Background/Aims: Few studies have been designed to directly investigate the exact mechanisms underlying the different phenotypes between cirrhotic and non-cirrhotic hepatocellular carcinoma (HCC). This study aimed to illuminate the incidence and developmental mechanisms for both types of HCC through differentially expressed microRNAs (miRNAs) using bioinformatic analysis. Methods: The miRNA-seq data and clinical data of patients (from The Cancer Genome Atlas (TCGA) database) were utilized to determine differentially expressed miRNAs between cirrhotic and non-cirrhotic HCC. Afterwards, the function of the selected miRNAs was predicted with online tools. Furthermore, the miRNA expression and clinical significance were validated by external datasets and our experiment. Results: The present study included 135 non-cirrhotic and 80 cirrhotic patients to find differentially expressed miRNAs. Among them, four miRNAs (mir-1296, mir-23c, mir-149, and mir-95) were finally selected for further validation and analysis. Correlation analysis found that two miRNAs are greatly associated with the non-cirrhotic HCC patients’ clinical traits, such as the T, M, and N tumor stages. However, only mir-23c was associated with the cirrhotic HCC patients’ tumor T and N stages. Furthermore, survival analysis revealed that increased mir-149 in non-cirrhotic HCC, patients’ age and the existence of vessels in the tumor in cirrhotic HCC were independent risk factors for the patients’ postoperative overall survival. Functional and interaction analyses also supported the notion that these miRNAs function through some pathways that influence the behavior of the HCC. These results are strongly supported by analysis of extra datasets and our experiment. Conclusions: The cirrhotic and non-cirrhotic HCC types involve differentially expressed miRNAs, which are correlated with distinctive pathological traits. To some extent, non-cirrhotic HCC seems more dependent on miRNA network regulation, but additional studies are needed to confirm this conclusion.

scholarly journals Mast Cells Resting-Related Prognostic Signature in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Hao Zhang ◽  
Lin Sun ◽  
Xiao Hu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mast Cells ◽  
Liver Cancer ◽  
Differentially Expressed Genes ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Immune Checkpoints ◽  
New Ideas ◽  
Cancer Genome Atlas

The immune microenvironment of liver cancer is of great significance for the treatment of liver cancer. After evaluating the content of mast cells resting in the transcriptome data of The Cancer Genome Atlas database by CIBERSORT analysis, this study aimed to group the samples according to the content of mast cells resting in different samples to find the differentially expressed genes in the two groups. Significant prognostic differences were found between high and low mast cells resting infiltration groups. The prognostic model was constructed according to the differentially expressed genes. The model was validated using external independent datasets. The results revealed that the constructed model was reliable. It could well distinguish the prognostic differences of patients in different characteristic groups. The high-risk group was mainly concentrated in metabolic pathways. The risk score of this model was closely related to some immune cells, immune function, and immune checkpoints. Therefore, this model may provide new ideas for immunotherapy of hepatocellular carcinoma.

scholarly journals Involvement of Differentially Expressed microRNAs in the PEGylated Liposome Encapsulated 188Rhenium-Mediated Suppression of Orthotopic Hypopharyngeal Tumor

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3609
Author(s):  
Bing-Ze Lin ◽  
Shen-Ying Wan ◽  
Min-Ying Lin ◽  
Chih-Hsien Chang ◽  
Ting-Wen Chen ◽  
...  
Keyword(s):  
Therapeutic Efficacy ◽  
Survival Rates ◽  
Clinical Information ◽  
Hypopharyngeal Cancer ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas ◽  
Cancer Genome Atlas ◽  
Next Generation Sequencing Ngs

Hypopharyngeal cancer (HPC) accounts for the lowest survival rate among all types of head and neck cancers (HNSCC). However, the therapeutic approach for HPC still needs to be investigated. In this study, a theranostic 188Re-liposome was prepared to treat orthotopic HPC tumors and analyze the deregulated microRNA expressive profiles. The therapeutic efficacy of 188Re-liposome on HPC tumors was evaluated using bioluminescent imaging followed by next generation sequencing (NGS) analysis, in order to address the deregulated microRNAs and associated signaling pathways. The differentially expressed microRNAs were also confirmed using clinical HNSCC samples and clinical information from The Cancer Genome Atlas (TCGA) database. Repeated doses of 188Re-liposome were administrated to tumor-bearing mice, and the tumor growth was apparently suppressed after treatment. For NGS analysis, 13 and 9 microRNAs were respectively up-regulated and down-regulated when the cutoffs of fold change were set to 5. Additionally, miR-206-3p and miR-142-5p represented the highest fold of up-regulation and down-regulation by 188Re-liposome, respectively. According to Differentially Expressed MiRNAs in human Cancers (dbDEMC) analysis, most of 188Re-liposome up-regulated microRNAs were categorized as tumor suppressors, while down-regulated microRNAs were oncogenic. The KEGG pathway analysis showed that cancer-related pathways and olfactory and taste transduction accounted for the top pathways affected by 188Re-liposome. 188Re-liposome down-regulated microRNAs, including miR-143, miR-6723, miR-944, and miR-136 were associated with lower survival rates at a high expressive level. 188Re-liposome could suppress the HPC tumors in vivo, and the therapeutic efficacy was associated with the deregulation of microRNAs that could be considered as a prognostic factor.

Identification of prognostic biomarkers of hepatocellular carcinoma via long noncoding RNA expression and copy number alterations

Epigenomics ◽  
2020 ◽  
Vol 12 (15) ◽  
pp. 1303-1315
Author(s):  
Weibo Du ◽  
Wenbiao Chen ◽  
Zheyue Shu ◽  
Dairong Xiang ◽  
Kefan Bi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Copy Number ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Prognostic Biomarkers ◽  
Copy Number Alterations ◽  
Sequencing Data ◽  
Cancer Genome Atlas

Aim: This study aimed to identify long noncoding RNAs (lncRNAs) with potential to be prognostic biomarkers of hepatocellular carcinoma (HCC) by analyzing copy number alterations (CNAs). Methods: RNA Sequencing data of 369 HCC patients was downloaded from The Cancer Genome Atlas database and analyzed with a series of systematic bioinformatics methods. Results: LncRNA-CNA association analysis revealed that many lncRNAs were located in sites frequently amplified or deleted. Three upregulated lncRNAs (LINC00689, SNHG20 and MAFG-AS1) with copy amplification and one downregulated lncRNA TMEM220-AS1 with copy deletion were associated with poor prognosis of HCC. Conclusion: This study reveals that differentially expressed lncRNAs correlate with CNAs in HCC. Moreover, the differentially expressed lncRNAs and their copy amplification/deletions could be promising prognostic biomarkers of HCC.

scholarly journals miR-10a and miR-204 as a Potential Prognostic Indicator in Low-Grade Gliomas

2017 ◽  
Vol 16 ◽  
pp. 117693511770287 ◽  
Author(s):  
Ju Cheol Son ◽  
Hyoung Oh Jeong ◽  
Deaui Park ◽  
Sang Gyoon No ◽  
Eun Kyeong Lee ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Target Genes ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Low Grade ◽  
Low Grade Gliomas ◽  
Clinical Biomarkers ◽  
Differentially Expressed Mirnas ◽  
Cancer Genome Atlas

This study aimed to identify and characterize microRNAs (miRNAs) that are related to radiosensitivity in low-grade gliomas (LGGs). The miRNA expression levels in radiosensitive and radioresistant LGGs were compared using The Cancer Genome Atlas database, and differentially expressed miRNAs were identified using the EBSeq package. The miRNA target genes were predicted using Web databases. Fifteen miRNAs were differentially expressed between the groups, with miR-10a and miR-204 being related to overall survival (OS) of patients with LGG. Patients with upregulated miR-10a expression had a higher mortality rate and shorter OS time, whereas patients with downregulated miR-204 expression had a lower mortality rate and longer OS time. Two genes, HSP90AA1 and CREB5, were targets for both miRNAs. Thus, this study suggests that expression of miR-10a and miR-204 is significantly related to both radiosensitivity and the survival of patients with LGG. These miRNAs could therefore act as clinical biomarkers for LGG prognosis and diagnosis.

Decreased expression of ARID1A invasively downregulates the expression of ribosomal proteins in hepatocellular carcinoma

2021 ◽  
Author(s):  
Jing Zhao ◽  
Weiran Xu ◽  
Yu Zhang ◽  
Xiaomin Lv ◽  
Yiran Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Cells ◽  
Ribosomal Proteins ◽  
Bioinformatic Analysis ◽  
The Cancer Genome Atlas ◽  
Reverse Transcription Pcr ◽  
Adaptive Mechanisms ◽  
Tumor Mutational Burden ◽  
Cancer Genome Atlas ◽  
Liver Hepatocellular Carcinoma

Background: There was increasing evidence showing that ARID1A alterations correlated with higher tumor mutational burden, but there were limited studies focusing on the adaptive mechanisms for tumor cells to survive under excessive genomic alterations. Materials & methods: To further explore the adaptive mechanisms under ARID1A alterations, we performed RNA sequencing in ARID1A knockdown hepatocellular carcinoma cell lines, and demonstrated that decreased expression of ARID1A controlled global ribosomal proteins synthesis. The results were further confirmed by quantitative reverse transcription-PCR and bioinformatic analysis in The Cancer Genome Atlas Liver Hepatocellular Carcinoma database. Conclusion: The present study was the first to demonstrate that ARID1A might be involved in the translation pathway and served as an adaptive mechanism for tumor cells to survive under stress.

scholarly journals Modularity of the metabolic gene network as a prognostic biomarker for hepatocellular carcinoma

2017 ◽  
Author(s):  
Fengdan Ye ◽  
Dongya Jia ◽  
Mingyang Lu ◽  
Herbert Levine ◽  
Michael W Deem
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Biomarker ◽  
Malignant Tumors ◽  
Aerobic Glycolysis ◽  
Expression Patterns ◽  
Cancer Recurrence ◽  
Metabolic Reprogramming ◽  
The Cancer Genome Atlas ◽  
Driver Genes ◽  
Tumor Stages

AbstractAbnormal metabolism is an emerging hallmark of cancer. Cancer cells utilize both aerobic glycolysis and oxidative phosphorylation (OXPHOS) for energy production and biomass synthesis. Understanding the metabolic reprogramming in cancer can help design therapies to target metabolism and thereby to improve prognosis. We have previously argued that more malignant tumors are usually characterized by a more modular expression pattern of cancer-associated genes. In this work, we analyzed the expression patterns of metabolism genes in terms of modularity for 371 hepatocellular carcinoma (HCC) samples from the Cancer Genome Atlas (TCGA). We found that higher modularity significantly correlated with glycolytic phenotype, later tumor stages, higher metastatic potential, and cancer recurrence, all of which contributed to poorer prognosis. Among patients with recurred tumor, we found the correlation of higher modularity with worse prognosis during early to mid-progression. Furthermore, we developed metrics to calculate individual modularity, which was shown to be predictive of cancer recurrence and patients’ survival and therefore may serve as a prognostic biomarker. Our overall conclusion is that more aggressive HCC tumors, as judged by decreased host survival probability, had more modular expression patterns of metabolic genes. These results may be used to identify cancer driver genes and for drug design.

scholarly journals CYSTM1: A Novel Biomarker for Hepatocellular Carcinoma Prognosis

2021 ◽  
Author(s):  
Jun Du ◽  
Jinguo Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Early Stage ◽  
Human Tumor ◽  
The Cancer Genome Atlas ◽  
Data Set ◽  
Kaplan Meier ◽  
Cancer Genome Atlas ◽  
Cox Proportional Hazard Regression ◽  
The Relationship

Abstract Background: The expression and molecular mechanism of cysteine rich transmembrane module containing 1 (CYSTM1) in human tumor cells remains unclear. The aim of this study was to determine whether CYSTM1 could be used as a potential prognostic biomarker for hepatocellular carcinoma (HCC).Methods: We first demonstrated the relationship between CYSTM1 expression and HCC in various public databases. Secondly, Kaplan–Meier analysis and Cox proportional hazard regression model were performed to evaluate the relationship between the expression of CYSTM1 and the survival of HCC patients which data was downloaded in the cancer genome atlas (TCGA) database. Finally, we used the expression data of CYSTM1 in TCGA database to predict CYSTM1-related signaling pathways through bioinformatics analysis.Results: The expression level of CYSTM1 in HCC tissues was significantly correlated with T stage (p = 0.039). In addition, Kaplan–Meier analysis showed that the expression of CYSTM1 was significantly associated with poor prognosis in patients with early-stage HCC (p = 0.003). Multivariate analysis indicated that CYSTM1 is a potential predictor of poor prognosis in HCC patients (p = 0.036). The results of biosynthesis analysis demonstrated that the data set of CYSTM1 high expression was mainly enriched in neurodegeneration and oxidative phosphorylation pathways.Conclusion: CYSTM1 is an effective biomarker for the prognosis of patients with early-stage HCC and may play a key role in the occurrence and progression of HCC.

scholarly journals Identification of Hypoxia-Related Differentially Expressed Genes and Construction of the Clinical Prognostic Predictor in Hepatocellular Carcinoma by Bioinformatic Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Hao Guo ◽  
Jing Zhou ◽  
Yanjun Zhang ◽  
Zhi Wang ◽  
Likun Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Model ◽  
Molecular Mechanisms ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Clinical Prognosis ◽  
Prognostic Predictor ◽  
Key Genes

Background. Hypoxia closely relates to malignant progression and appears to be prognostic for outcome in hepatocellular carcinoma (HCC). Our research is aimed at mining the hypoxic-related genes (HRGs) and constructing a prognostic predictor (PP) model on clinical prognosis in HCC patients. Methods. RNA-sequencing data about HRGs and clinical data of patients with HCC were obtained from The Cancer Genome Atlas (TCGA) database portal. Differentially expressed HRGs between HCC and para-carcinoma tissue samples were obtained by applying the Wilcox analysis in R statistical software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene functional enrichment analyses. Then, the patients who were asked to follow up for at least one month were enrolled in the following study. Cox proportional risk regression model was applied to obtain key HRGs which related to overall survival (OS) in HCC. PP was constructed and defined, and the accuracy of PP was validated by constructing the signature in a training set and validation set. Connectivity map (CMap) was used to find potential drugs, and gene set cancer analysis (GSCA) was also performed to explore the underlying molecular mechanisms. Results. Thirty-seven differentially expressed HRGs were obtained. It contained 28 upregulated and 9 downregulated genes. After the univariate Cox regression model analysis, we obtained 27 prognosis-related HRGs. Of these, 25 genes were risk factors for cancer, and 2 genes were protective factors. The PP was composed by 12 key genes (HDLBP, SAP30, PFKP, DPYSL4, SLC2A1, HMOX1, PGK1, ERO1A, LDHA, ENO2, SLC6A6, and TPI1). GSCA results showed the overall activity of these 12 key genes in 10 cancer-related pathways. Besides, CMap identified deferoxamine, crotamiton, talampicillin, and lycorine might have effects with HCC. Conclusions. This study firstly reported 12 prognostic HRGs and constructed the model of the PP. This comprehensive research of multiple databases helps us gain insight into the biological properties of HCC and provides deferoxamine, crotamiton, talampicillin, and lycorine as potential drugs to fight against HCC.

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