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Tytuł pozycji:

Comprehensive analysis of transcriptome profiles in hepatocellular carcinoma

Tytuł:
Comprehensive analysis of transcriptome profiles in hepatocellular carcinoma
Autorzy:
Yu Jin
Wai Yeow Lee
Soo Ting Toh
Chandana Tennakoon
Han Chong Toh
Pierce Kah-Hoe Chow
Alexander Y.-F. Chung
Samuel S. Chong
London L.-P.-J. Ooi
Wing-Kin Sung
Caroline G.-L. Lee
Temat:
Liver cancer
HBV integration
Chimeric transcripts
Differentially expressed genes
Somatic mutations
Medicine
Źródło:
Journal of Translational Medicine, Vol 17, Iss 1, Pp 1-16 (2019)
Wydawca:
BMC, 2019.
Rok publikacji:
2019
Kolekcja:
LCC:Medicine
Typ dokumentu:
article
Opis pliku:
electronic resource
Język:
English
ISSN:
1479-5876
Relacje:
http://link.springer.com/article/10.1186/s12967-019-2025-x; https://doaj.org/toc/1479-5876
DOI:
10.1186/s12967-019-2025-x
Dostęp URL:
https://doaj.org/article/6c26ddd30b8844ce8595ebdb5c208db6  Link otwiera się w nowym oknie
Numer akcesji:
edsdoj.6c26ddd30b8844ce8595ebdb5c208db6
Czasopismo naukowe
Abstract 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.
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