Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study

The incidence and mortality of hepatocellular carcinoma (HCC) in Sub-Saharan Africa is projected to increase sharply by 2040 against a backdrop of limited diagnostic and therapeutic options. Two large South African-based case control studies have developed a serum-based miRNome for Hepatitis B-assoc...

Full description

Bibliographic Details
Main Authors: Kurt Sartorius, Benn Sartorius, Cheryl Winkler, Anil Chuturgoon, Tsai-Wei Shen, Yongmei Zhao, Ping An
Format: Article
Language:English
Published: MDPI AG 2024-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/25/2/975
_version_ 1797339835214594048
author Kurt Sartorius
Benn Sartorius
Cheryl Winkler
Anil Chuturgoon
Tsai-Wei Shen
Yongmei Zhao
Ping An
author_facet Kurt Sartorius
Benn Sartorius
Cheryl Winkler
Anil Chuturgoon
Tsai-Wei Shen
Yongmei Zhao
Ping An
author_sort Kurt Sartorius
collection DOAJ
description The incidence and mortality of hepatocellular carcinoma (HCC) in Sub-Saharan Africa is projected to increase sharply by 2040 against a backdrop of limited diagnostic and therapeutic options. Two large South African-based case control studies have developed a serum-based miRNome for Hepatitis B-associated hepatocellular carcinoma (HBV-HCC), as well as identifying their gene targets and pathways. Using a combination of RNA sequencing, differential analysis and filters including a unique molecular index count (UMI) ≥ 10 and log fold change (LFC) range > 2: <−0.5 (<i>p</i> < 0.05), 91 dysregulated miRNAs were characterized including 30 that were upregulated and 61 were downregulated. KEGG analysis, a literature review and other bioinformatic tools identified the targeted genes and HBV-HCC pathways of the top 10 most dysregulated miRNAs. The results, which are based on differentiating miRNA expression of cases versus controls, also develop a serum-based miRNA diagnostic panel that indicates 95.9% sensitivity, 91.0% specificity and a Youden Index of 0.869. In conclusion, the results develop a comprehensive African HBV-HCC miRNome that potentially can contribute to RNA-based diagnostic and therapeutic options.
first_indexed 2024-03-08T09:54:09Z
format Article
id doaj.art-bdffa2a7633e430f95025ef1526f30ac
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-08T09:54:09Z
publishDate 2024-01-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-bdffa2a7633e430f95025ef1526f30ac2024-01-29T13:55:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-0125297510.3390/ijms25020975Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African StudyKurt Sartorius0Benn Sartorius1Cheryl Winkler2Anil Chuturgoon3Tsai-Wei Shen4Yongmei Zhao5Ping An6Faculty of Commerce, Law and Management, University of the Witwatersrand, Johannesburg 2001, South AfricaSchool of Public Health, University of Queensland, Brisbane, QLD 4102, AustraliaCentre for Cancer Research, Basic Research Laboratory, National Cancer Institute, Frederick Natifol Laboratory for Cancer Research, National Institute of Health, Frederick, MD 21701, USASchool of Laboratory Medicine and Molecular Sciences, University of Kwazulu-Natal, Durban 4041, South AfricaCCR-SF Bioinformatics Group, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USACCR-SF Bioinformatics Group, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USACentre for Cancer Research, Basic Research Laboratory, National Cancer Institute, Frederick Natifol Laboratory for Cancer Research, National Institute of Health, Frederick, MD 21701, USAThe incidence and mortality of hepatocellular carcinoma (HCC) in Sub-Saharan Africa is projected to increase sharply by 2040 against a backdrop of limited diagnostic and therapeutic options. Two large South African-based case control studies have developed a serum-based miRNome for Hepatitis B-associated hepatocellular carcinoma (HBV-HCC), as well as identifying their gene targets and pathways. Using a combination of RNA sequencing, differential analysis and filters including a unique molecular index count (UMI) ≥ 10 and log fold change (LFC) range > 2: <−0.5 (<i>p</i> < 0.05), 91 dysregulated miRNAs were characterized including 30 that were upregulated and 61 were downregulated. KEGG analysis, a literature review and other bioinformatic tools identified the targeted genes and HBV-HCC pathways of the top 10 most dysregulated miRNAs. The results, which are based on differentiating miRNA expression of cases versus controls, also develop a serum-based miRNA diagnostic panel that indicates 95.9% sensitivity, 91.0% specificity and a Youden Index of 0.869. In conclusion, the results develop a comprehensive African HBV-HCC miRNome that potentially can contribute to RNA-based diagnostic and therapeutic options.https://www.mdpi.com/1422-0067/25/2/975microRNA (miRNA)dysregulatedmodulategene targetspathwayshepatitis B-associated carcinoma (HBV-HCC)
spellingShingle Kurt Sartorius
Benn Sartorius
Cheryl Winkler
Anil Chuturgoon
Tsai-Wei Shen
Yongmei Zhao
Ping An
Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study
International Journal of Molecular Sciences
microRNA (miRNA)
dysregulated
modulate
gene targets
pathways
hepatitis B-associated carcinoma (HBV-HCC)
title Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study
title_full Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study
title_fullStr Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study
title_full_unstemmed Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study
title_short Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study
title_sort serum microrna profiles and pathways in hepatitis b associated hepatocellular carcinoma a south african study
topic microRNA (miRNA)
dysregulated
modulate
gene targets
pathways
hepatitis B-associated carcinoma (HBV-HCC)
url https://www.mdpi.com/1422-0067/25/2/975
work_keys_str_mv AT kurtsartorius serummicrornaprofilesandpathwaysinhepatitisbassociatedhepatocellularcarcinomaasouthafricanstudy
AT bennsartorius serummicrornaprofilesandpathwaysinhepatitisbassociatedhepatocellularcarcinomaasouthafricanstudy
AT cherylwinkler serummicrornaprofilesandpathwaysinhepatitisbassociatedhepatocellularcarcinomaasouthafricanstudy
AT anilchuturgoon serummicrornaprofilesandpathwaysinhepatitisbassociatedhepatocellularcarcinomaasouthafricanstudy
AT tsaiweishen serummicrornaprofilesandpathwaysinhepatitisbassociatedhepatocellularcarcinomaasouthafricanstudy
AT yongmeizhao serummicrornaprofilesandpathwaysinhepatitisbassociatedhepatocellularcarcinomaasouthafricanstudy
AT pingan serummicrornaprofilesandpathwaysinhepatitisbassociatedhepatocellularcarcinomaasouthafricanstudy