title: Genome-wide and differential proteomic analysis of hepatitis B virus and aflatoxin B1 related hepatocellular carcinoma in Guangxi, China.
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 observered, 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.
authors.affiliation: Department of Hepatobiliary Surgery, Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
authors.forename: Lu-Nan
authors.initials: LN
authors.lastname: Qi
authors.affiliation: Department of Hepatobiliary Surgery, Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
authors.forename: Le-Qun
authors.initials: LQ
authors.lastname: Li
authors.affiliation: Department of Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary Surgery, Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
authors.forename: Zhao-Hong
authors.initials: ZH
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary Surgery, Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Bai
authors.affiliation: Department of Hepatobiliary Surgery, Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
authors.forename: Bang-De
authors.initials: BD
authors.lastname: Xiang
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
authors.forename: Kai-Yin
authors.initials: KY
authors.lastname: Xiao
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
authors.forename: Min-Hao
authors.initials: MH
authors.lastname: Peng
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
authors.forename: Tang-Wei
authors.initials: TW
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.affiliation: China National Human Genome Center at Shanghai, Shanghai, China.
authors.forename: Ze-Guang
authors.initials: ZG
authors.lastname: Han
authors.affiliation: Department of Urology and Nephrology Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
authors.forename: Zeng-Nan
authors.initials: ZN
authors.lastname: Mo
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, United States of America.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
authors.affiliation: Laboratory of Genomic Diversity, National Cancer Institute, NIH, Frederick, Maryland, United States of America.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Winkler
authors.affiliation: Laboratory of Genomic Diversity, National Cancer Institute, NIH, Frederick, Maryland, United States of America.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China ; Laboratory of Genomic Diversity, National Cancer Institute, NIH, Frederick, Maryland, United States of America.
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
mesh_terms: D000328:Adult; D016604:Aflatoxin B1 / Q000633:toxicity*; D000368:Aged; D000449:Aldehyde Reductase / Q000235:genetics* / Q000378:metabolism; D000074408:Aldo-Keto Reductases; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics* / Q000378:metabolism; D002681:China; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D018572:Disease-Free Survival; D005260:Female; D018628:Gene Dosage; D006515:Hepatitis B virus / Q000472:pathogenicity*; D019694:Hepatitis B, Chronic / Q000150:complications; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012306:Risk; D055815:Young Adult
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016604:Aflatoxin B1; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase