Biology Faculty Articles
Document Type
Article
Publication Date
12-2013
Publication Title
PLoS ONE
ISSN
1932-6203
Volume
8
Issue/No.
12 e83465
First Page
1
Last Page
15
Abstract
Both hepatitis B virus (HBV) and aflatoxin B1 (AFB1) exposure can cause liver damage as well as increase the probability of hepatocellular carcinoma (HCC). To investigate the underlying genetic changes that may influence development of HCC associated with HBV infection and AFB1 exposure, HCC patients were subdivided into 4 groups depending upon HBV and AFB1 exposure status: (HBV(+)/AFB1(+), HBV(+)/AFB1(-), HBV(-)/AFB1(+), HBV(-)/AFB1(-)). Genetic abnormalities and protein expression profiles were analyzed by array-based comparative genomic hybridization and isobaric tagging for quantitation. A total of 573 chromosomal aberrations (CNAs) including 184 increased and 389 decreased were detected in our study population. Twenty-five recurrently altered regions (RARs; chromosomal alterations observed in ≥10 patients) in chromosomes were identified. Loss of 4q13.3-q35.2, 13q12.1-q21.2 and gain of 7q11.2-q35 were observed with a higher frequency in the HBV(+)/AFB1(+), HBV(+)/AFB1(-) and HBV(-)/AFB1(+) groups compared to the HBV(-)/AFB(-) group. Loss of 8p12-p23.2 was associated with high TNM stage tumors (P = 0.038) and was an unfavorable prognostic factor for tumor-free survival (P=0.045). A total of 133 differentially expressed proteins were identified in iTRAQ proteomics analysis, 69 (51.8%) of which mapped within identified RARs. The most common biological processes affected by HBV and AFB1 status in HCC tumorigenesis were detoxification and drug metabolism pathways, antigen processing and anti-apoptosis pathways. Expression of AKR1B10 was increased significantly in the HBV(+)/AFB1(+) and HBV(-)/AFB1(+) groups. A significant correlation between the expression of AKR1B10 mRNA and protein levels as well as AKR1B10 copy number was observed, which suggest that AKR1B10 may play a role in AFB1-related hepatocarcinogenesis. In summary, a number of genetic and gene expression alterations were found to be associated with HBV and AFB1- related HCC. The possible synergistic effects of HBV and AFB1 in hepatocarcinogenesis warrant further investigations.
Additional Comments
National Nature Science Foundation of China grant #s: NSFC 81072321, 30960021, 30460143, 30560133; Guangxi Nature Sciences Grant #s: GKJ 0236030,0632007-1E, 0640101, GKG 0592007-1A; Guangxi Health Ministry Medicine grant #: Z2010108; National Institutes of Health grant #s: ES05116, ES09089
NSUWorks Citation
Qi, Lu-Nan; Le-Qun Qi; Yuan-Yuan Chen; Zhao-Hong Chen; Tao Bai; Bang-De Xiang; Xiao Qin; Kai-Yin Xiao; Min-Hao Peng; Zhi-Ming Liu; Tang-Wei Liu; Xue Qin; Shan Li; Ze-Guang Han; Zeng-Nan Mo; Regina M. Santella; Cheryl Winkler; Stephen J. O'Brien; and Tao Peng. 2013. "Genome-Wide and Differential Proteomic Analysis of Hepatitis B Virus and Aflatoxin B1 Related Hepatocellular Carcinoma in Guangxi, China." PLoS ONE 8, (12 e83465): 1-15. https://nsuworks.nova.edu/cnso_bio_facarticles/736
ORCID ID
0000-0001-7353-8301
ResearcherID
N-1726-2015
Included in
Genetics and Genomics Commons, Immunology and Infectious Disease Commons, Medicine and Health Sciences Commons
Comments
© 2013 Qi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.