Genome-wide and differential proteomic analysis of hepatitis B virus and aflatoxin B1 related hepatocellular carcinoma in Guangxi, China.
Genome-wide and differential proteomic analysis of hepatitis B virus and aflatoxin B1 related hepatocellular carcinoma in Guangxi, China.
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DOI：
10.1371/journal.pone.0083465
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Peng T
中科院分区：
文献类型：
--
作者：
Qi LN;Li LQ;Chen YY;Chen ZH;Bai T;Xiang BD;Qin X;Xiao KY;Peng MH;Liu ZM;Liu TW;Qin X;Li S;Han ZG;Mo ZN;Santella RM;Winkler CA;O'Brien SJ;Peng T
乙型肝炎病毒（HBV）和黄曲霉毒素B1 （AFB1）暴露均可导致肝损伤，并增加肝细胞癌（HCC）的可能性。为了研究可能影响与HBV感染和AFB1暴露相关的HCC发展的潜在遗传变化，HCC患者根据HBV和AFB1暴露状态细分为4组：(HBV(+)/AFB1(+)， HBV(+)/AFB1(-)， HBV(-)/AFB1(+)， HBV（-)/AFB1(-)）。通过阵列比较基因组杂交和等压标记定量分析遗传异常和蛋白质表达谱。本研究共检出573例染色体畸变（CNAs），其中增高184例，降低389例。在染色体中鉴定出25个经常性改变区域（RARs；在≥10例患者中观察到染色体改变）。与HBV(-)/AFB（-）组相比，HBV(+)/AFB1（+）、HBV(+)/AFB1（-）和HBV(-)/AFB1（+）组中4q13.3-q35.2、13q12.1-q21.2缺失和7q11.2-q35增加的频率更高。8p12-p23.2缺失与高TNM期肿瘤相关（P = 0.038），是无肿瘤生存的不利预后因素（P =0.045）。iTRAQ蛋白质组学分析共鉴定出133个差异表达蛋白，其中69个（51.8%）位于鉴定的RARs内。在HCC发生过程中，受HBV和AFB1状态影响最常见的生物学过程是解毒和药物代谢途径、抗原加工和抗凋亡途径。在HBV(+)/AFB1（+）和HBV(-)/AFB1（+）组中，AKR1B10的表达显著升高。我们观察到AKR1B10 mRNA的表达与蛋白水平以及AKR1B10拷贝数有显著的相关性，提示AKR1B10可能在afb1相关的肝癌发生中发挥作用。总之，许多遗传和基因表达改变被发现与HBV和AFB1相关的HCC有关。HBV和AFB1在肝癌发生中可能的协同作用值得进一步研究。
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.
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