Transcriptomic Analyses Reveal Long Non-Coding RNA in Peripheral Blood Mononuclear Cells as a Novel Biomarker for Diagnosis and Prognosis of Hepatocellular Carcinoma

Novel biomarkers are highly required for the diagnosis and predicting prognosis of hepatocellular carcinoma (HCC). In this study, we investigated the profiles of long non-coding RNAs (lncRNAs) obtained from the peripheral blood mononuclear cells (PBMCs) of patients with HCC and PBMCs from a co-cultu...

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Main Authors: Pattapon Kunadirek, Nutcha Pinjaroen, Intawat Nookaew, Pisit Tangkijvanich, Natthaya Chuaypen
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/14/7882
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author Pattapon Kunadirek
Nutcha Pinjaroen
Intawat Nookaew
Pisit Tangkijvanich
Natthaya Chuaypen
author_facet Pattapon Kunadirek
Nutcha Pinjaroen
Intawat Nookaew
Pisit Tangkijvanich
Natthaya Chuaypen
author_sort Pattapon Kunadirek
collection DOAJ
description Novel biomarkers are highly required for the diagnosis and predicting prognosis of hepatocellular carcinoma (HCC). In this study, we investigated the profiles of long non-coding RNAs (lncRNAs) obtained from the peripheral blood mononuclear cells (PBMCs) of patients with HCC and PBMCs from a co-culture model using transcriptomic analysis. The differentially expressed lncRNAs (DElncRNAs) were then characterized and integrated as cancer-induced lncRNAs. Among them, three up-regulating DElncRNAs including <i>MIR4435-2HG</i>, <i>SNHG9</i> and <i>lnc-LCP2-1</i> and one down-regulating, <i>lnc-POLD3-2</i>, were identified. The functional analysis showed that these enriched lncRNAs were mainly associated with carcinogenesis and immune responses. Following further validation in PBMCs samples (100 HBV-related HCC, 100 chronic hepatitis B and 100 healthy controls), <i>MIR4435-2HG</i>, <i>lnc-POLD3-2</i> and their combination were revealed to be sensitive biomarkers in discriminating HCC from non-HCC (AUROC = 0.78, 0.80, and 0.87, respectively), particularly among individuals with normal serum alpha-fetoprotein levels. Additionally, high circulating <i>SNHG9</i> expression was shown to be an independent prognostic factor of overall survival in patients with HCC. These results indicate that determining these lncRNAs in PBMCs could serve as novel diagnostic and prognostic biomarkers for HBV-related HCC.
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spelling doaj.art-5f22ff86f47a447d84d6da6572118f512023-11-30T21:06:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012314788210.3390/ijms23147882Transcriptomic Analyses Reveal Long Non-Coding RNA in Peripheral Blood Mononuclear Cells as a Novel Biomarker for Diagnosis and Prognosis of Hepatocellular CarcinomaPattapon Kunadirek0Nutcha Pinjaroen1Intawat Nookaew2Pisit Tangkijvanich3Natthaya Chuaypen4Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Biomedical Informatics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USACenter of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandCenter of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandNovel biomarkers are highly required for the diagnosis and predicting prognosis of hepatocellular carcinoma (HCC). In this study, we investigated the profiles of long non-coding RNAs (lncRNAs) obtained from the peripheral blood mononuclear cells (PBMCs) of patients with HCC and PBMCs from a co-culture model using transcriptomic analysis. The differentially expressed lncRNAs (DElncRNAs) were then characterized and integrated as cancer-induced lncRNAs. Among them, three up-regulating DElncRNAs including <i>MIR4435-2HG</i>, <i>SNHG9</i> and <i>lnc-LCP2-1</i> and one down-regulating, <i>lnc-POLD3-2</i>, were identified. The functional analysis showed that these enriched lncRNAs were mainly associated with carcinogenesis and immune responses. Following further validation in PBMCs samples (100 HBV-related HCC, 100 chronic hepatitis B and 100 healthy controls), <i>MIR4435-2HG</i>, <i>lnc-POLD3-2</i> and their combination were revealed to be sensitive biomarkers in discriminating HCC from non-HCC (AUROC = 0.78, 0.80, and 0.87, respectively), particularly among individuals with normal serum alpha-fetoprotein levels. Additionally, high circulating <i>SNHG9</i> expression was shown to be an independent prognostic factor of overall survival in patients with HCC. These results indicate that determining these lncRNAs in PBMCs could serve as novel diagnostic and prognostic biomarkers for HBV-related HCC.https://www.mdpi.com/1422-0067/23/14/7882hepatocellular carcinomaperipheral blood mononuclear cellstranscriptomic profilelong non-coding RNAbiomarkeralpha-fetoprotein
spellingShingle Pattapon Kunadirek
Nutcha Pinjaroen
Intawat Nookaew
Pisit Tangkijvanich
Natthaya Chuaypen
Transcriptomic Analyses Reveal Long Non-Coding RNA in Peripheral Blood Mononuclear Cells as a Novel Biomarker for Diagnosis and Prognosis of Hepatocellular Carcinoma
International Journal of Molecular Sciences
hepatocellular carcinoma
peripheral blood mononuclear cells
transcriptomic profile
long non-coding RNA
biomarker
alpha-fetoprotein
title Transcriptomic Analyses Reveal Long Non-Coding RNA in Peripheral Blood Mononuclear Cells as a Novel Biomarker for Diagnosis and Prognosis of Hepatocellular Carcinoma
title_full Transcriptomic Analyses Reveal Long Non-Coding RNA in Peripheral Blood Mononuclear Cells as a Novel Biomarker for Diagnosis and Prognosis of Hepatocellular Carcinoma
title_fullStr Transcriptomic Analyses Reveal Long Non-Coding RNA in Peripheral Blood Mononuclear Cells as a Novel Biomarker for Diagnosis and Prognosis of Hepatocellular Carcinoma
title_full_unstemmed Transcriptomic Analyses Reveal Long Non-Coding RNA in Peripheral Blood Mononuclear Cells as a Novel Biomarker for Diagnosis and Prognosis of Hepatocellular Carcinoma
title_short Transcriptomic Analyses Reveal Long Non-Coding RNA in Peripheral Blood Mononuclear Cells as a Novel Biomarker for Diagnosis and Prognosis of Hepatocellular Carcinoma
title_sort transcriptomic analyses reveal long non coding rna in peripheral blood mononuclear cells as a novel biomarker for diagnosis and prognosis of hepatocellular carcinoma
topic hepatocellular carcinoma
peripheral blood mononuclear cells
transcriptomic profile
long non-coding RNA
biomarker
alpha-fetoprotein
url https://www.mdpi.com/1422-0067/23/14/7882
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