Dataset Information

Comprehensive analysis of key lncRNAs in HCV-positive hepatocellular carcinoma.

ABSTRACT:

Introduction

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Despite the therapeutic advances in HCC in the past few decades, the mortality rate of HCC is still high. Hepatitis C (HCV) infection is one of the major etiological risk factors of HCCs. However, the underlying mechanisms of HCV-induced hepatocarcinogenesis remain largely unclear.

Material and methods

Our study represented the comprehensive analysis of differentially expressed lncRNAs in HCV-positive HCC for the first time by analyzing the public dataset GSE17856. Co-expression network and gene ontology (GO) analysis revealed the functions of those differentially expressed lncRNAs.

Results

We identified 256 upregulated lncRNAs and 198 downregulated lncRNAs in HCV- positive HCC compared to the normal liver tissues. Co-expression network and GO analysis showed that these lncRNAs were involved in regulating metabolism, energy pathways, proliferation and the immune response. Seven lncRNAs (LOC341056, CCT6P1, PTTG3P, LOC643387, LOC100133920, C3P1 and C22orf45) were identified as key lncRNAs and co-expressed with more than 100 differentially expressed genes (DEGs) in HCV-related HCC. Kaplan-Meier analysis showed that higher expression levels of LOC643387, PTTG3P, LOC341056, CCT6P1 and lower expression levels of C3P1 and C22orf45 were associated with shorter survival time in the TCGA dataset.

Conclusions

We believe that this study can provide novel potential therapeutic and prognostic biomarkers for HCV-positive HCC.

SUBMITTER: Liu J

PROVIDER: S-EPMC7811325 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Comprehensive analysis of key lncRNAs in HCV-positive hepatocellular carcinoma.

Liu Jingqi J Chen Ligang L Pan Jinshui J Chen Meiya M Zhou Jingping J Zhou Fei F Chen Peizhong P Song Yang Y

Archives of medical science : AMS 20201105 1

<h4>Introduction</h4>Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Despite the therapeutic advances in HCC in the past few decades, the mortality rate of HCC is still high. Hepatitis C (HCV) infection is one of the major etiological risk factors of HCCs. However, the underlying mechanisms of HCV-induced hepatocarcinogenesis remain largely unclear.<h4>Material and methods</h4>Our study represented the comprehensive analysis of differentially expressed lncRNAs in HCV- ...[more]

PMID: 33488867

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Project description:BACKGROUND:Hepatocellular carcinoma is the second most deadly cancer with late presentation and limited treatment options, highlighting an urgent need to better understand HCC to facilitate the identification of early-stage biomarkers and uncover therapeutic targets for the development of novel therapies for HCC. METHODS:Deep transcriptome sequencing of tumor and paired non-tumor liver tissues was performed to comprehensively evaluate the profiles of both the host and HBV transcripts in HCC patients. Differential gene expression patterns and the dys-regulated genes associated with clinical outcomes were analyzed. Somatic mutations were identified from the sequencing data and the deleterious mutations were predicted. Lastly, human-HBV chimeric transcripts were identified, and their distribution, potential function and expression association were analyzed. RESULTS:Expression profiling identified the significantly upregulated TP73 as a nodal molecule modulating expression of apoptotic genes. Approximately 2.5% of dysregulated genes significantly correlated with HCC clinical characteristics. Of the 110 identified genes, those involved in post-translational modification, cell division and/or transcriptional regulation were upregulated, while those involved in redox reactions were downregulated in tumors of patients with poor prognosis. Mutation signature analysis identified that somatic mutations in HCC tumors were mainly non-synonymous, frequently affecting genes in the micro-environment and cancer pathways. Recurrent mutations occur mainly in ribosomal genes. The most frequently mutated genes were generally associated with a poorer clinical prognosis. Lastly, transcriptome sequencing suggest that HBV replication in the tumors of HCC patients is rare. HBV-human fusion transcripts are a common observation, with favored HBV and host insertion sites being the HBx C-terminus and gene introns (in tumors) and introns/intergenic-regions (in non-tumors), respectively. HBV-fused genes in tumors were mainly involved in RNA binding while those in non-tumors tissues varied widely. These observations suggest that while HBV may integrate randomly during chronic infection, selective expression of functional chimeric transcripts may occur during tumorigenesis. CONCLUSIONS:Transcriptome sequencing of HCC patients reveals key cancer molecules and clinically relevant pathways deregulated/mutated in HCC patients and suggests that while HBV may integrate randomly during chronic infection, selective expression of functional chimeric transcripts likely occur during the process of tumorigenesis.

Project description:Molecular characterization of the CD133+ stem cells associated with hepatocarinogensis through identifying the expression patterns of specific microRNAs (miRNAs).We investigated the expression pattern of 13 miRNAs in purified CD133+ cells separated from the peripheral blood of healthy volunteers, chronic hepatitis C (CHC), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) patients a long with bone marrow samples from the healthy volunteers and the LC patients using custom miScript miRNA PCR array.The differential expression of the 13 studied miRNAs in CD133+ cells separated from the HCC patients' peripheral blood compared to the controls revealed that miR-602, miR-181b, miR-101, miR-122, miR-192, miR-125a-5p, and miR-221 were significantly up regulated (fold change = 1.8, 1.7, 2, 5.4, 1.6, 2.9 & 1.5 P value = 0.039, 0.0019, 0.0013, 0.0370, 00024, 0.000044 &0.000007 respectively). As for the HCC group compared to the CHC group; miR-602, miR-122, miR-181b, miR-125a-5p, and miR-192 were significantly up regulated (fold change = 13, 3.1, 2.8, 1.6 & 1.56, P value = 0.01, 0.001, 0.000004, 0.002 & 0.007 respectively). Upon comparing the HCC group to the LC group; miR-199a-3p, miR-192, miR-122, miR-181b, miR-224, miR-125a-5p, and miR-885-5p were significantly up regulated (fold change = 5, 6.7, 2.3, 3, 2.5, 4.2 & 39.5 P value = 0.001025, 0.000024, 0.000472, 0.000278, 0.000004, 0.000075 & 0.0000001 respectively) whereas miR-22 was significantly down regulated (fold change = 0.57 P value = 0.00002). Only, miR-192, miR-122, miR-181b and miR-125a-5p were significant common miRNAs in CD133+ cells of the HCC group compared to the other non-malignant groups.We identified a miRNA panel comprised of four miRNAs (miR-192, miR-122, miR-181b and miR-125a-5p) that may serve as a molecular tool for characterization of the CD133+ cells associated with different stages of hepatocarinogensis. This panel may aid in developing a new target therapy specific for those CD133+ cells.

Dataset Information

Comprehensive analysis of key lncRNAs in HCV-positive hepatocellular carcinoma.

Introduction

Material and methods

Results

Conclusions

Publications

Comprehensive analysis of key lncRNAs in HCV-positive hepatocellular carcinoma.

Similar Datasets

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