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Identification of characteristic TRB V usage in HBV-associated HCC by using differential expression profiling analysis.

ABSTRACT: Liver cancer is one of the most common cancers worldwide. CDR3 sequencing-based immune repertoire can be closely associated with cancer prognosis and development. Identifying the specific interaction between the TCR and cellular antigens is important for developing novel immunotherapeutic approaches for the treatment of cancer. The rearranged TCR? loci amplified using V?- and J?-specific primers by multi-PCR and sequenced using high-throughput sequencing (HTS) in liver cancers were compared with those of T cells from healthy adult peripheral blood and from adjacent liver tissue. The T-cell repertoires within each tumor show strong similarity to one another but are distinct from those of the circulating T-cell repertoire. In addition, our results demonstrate that there are significant differences in the T-cell repertoires of HCC (hepatocellular carcinoma), ICC (intrahepatic cholangiocarcinoma), and MHC (mixed hepatocellular and cholangiocellular carcinoma). Furthermore, we found that the highly expanded clone (HEC) ratio in blood samples from liver cancer patients differed significantly from those in the blood of healthy adults and hepatitis patients (p < 0.001). The above results suggest that comparison of the T-cell repertoires of tissue and blood could be used to distinguish liver cancer patients from healthy adults and from hepatitis patients. In the future, the diversity of CDR3 sequences in liver cancer may prove to be a useful and novel biomarker for detecting aggressive tumors with high invasive or metastatic capacity.

SUBMITTER: Han Y

PROVIDER: S-EPMC4570125 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Identification of characteristic TRB V usage in HBV-associated HCC by using differential expression profiling analysis.

Han Yingxin Y Liu Xing X Wang Yuqi Y Wu Xiaolei X Guan Yanfang Y Li Hongmei H Chen Xinchun X Zhou Boping B Yuan Qing Q Ou Ying Y Wu Renhua R Huang Wanqiu W Wang Yun Y Zhang Ming M Zhang Yinxin Y Zhu Dongxing D Zhu Hongmei H Yang Ling L Yi Xin X Huang Chen C Huang Jian J

Oncoimmunology 20150402 8

Liver cancer is one of the most common cancers worldwide. CDR3 sequencing-based immune repertoire can be closely associated with cancer prognosis and development. Identifying the specific interaction between the TCR and cellular antigens is important for developing novel immunotherapeutic approaches for the treatment of cancer. The rearranged TCRβ loci amplified using Vβ- and Jβ-specific primers by multi-PCR and sequenced using high-throughput sequencing (HTS) in liver cancers were compared with ...[more]

PMID: 26405574

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Project description:BackgroundHepatitis B virus (HBV) is one of the major risk factors of hepatocellular carcinoma (HCC). Increasing evidence indicates that microRNA (miRNA)-mRNA axis is involved in HCC. However, a comprehensive miRNA-mRNA regulatory network in HBV-related HCC is still absent. This study aims to identify potential miRNA-mRNA regulatory pathways contributing to pathogenesis of HBV-related HCC.MethodsMicroarray GSE69580 was downloaded from Gene Expression Omnibus (GEO) database. GEO2R and 'R-limma' were used to conduct differential expression analysis. The common miRNAs appeared in the two analytic sets were screened as potential differentially expressed miRNAs (DE-miRNAs). The prognostic roles of screened DE-miRNAs in HCC were further evaluated using Kaplan-Meier plotter database. Target genes of DE-miRNAs were predicted by miRNet. Then, protein-protein interaction (PPI) networks were established for these targets via the STRING database, after which hub genes in the networks were identified by Cytoscape. Functional annotation and pathway enrichment analyses for the target genes were performed through DAVID database. Three enriched pathways related to HBV-related HCC were selected for further analysis and potential target genes commonly appeared in all three pathways were screened. Cytoscape was employed to construct miRNA-hub gene network. The expression and correlation of potential miRNAs and targets were further detected in clinical HBV-related HCC samples by qRT-PCR.Results7 upregulated and 9 downregulated DE-miRNAs were accessed. 5 of 7 upregulated DE-miRNAs and 5 of 7 downregulated DE-miRNAs indicated significant prognostic roles in HCC. 2312 and 1175 target genes were predicted for the upregulated and downregulated DE-miRNAs, respectively. TP53 was identified as the hub gene in the PPI networks. Pathway enrichment analysis suggested that these predicted targets were linked to hepatitis B, pathways in cancer, microRNAs in cancer and viral carcinogenesis. Further analysis of these pathways screened 20 and 16 target genes for upregulated and downregulated DE-miRNAs, respectively. By detecting the expression of 36 target genes, six candidate target genes were identified. Finally, a potential miRNA-mRNA regulatory network was established based on the results of qRT-PCR and expression correlation analysis.ConclusionsIn the study, potential miRNA-mRNA regulatory pathways were identified, exploring the underlying pathogenesis and effective therapy strategy of HBV-related HCC.

Dataset Information

Identification of characteristic TRB V usage in HBV-associated HCC by using differential expression profiling analysis.

Publications

Identification of characteristic TRB V usage in HBV-associated HCC by using differential expression profiling analysis.

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