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P62 在乙型肝炎病毒感染和黄曲霉毒素 B1 暴露相关的肝细胞癌中的表达。

Expression of P62 in hepatocellular carcinoma involving hepatitis B virus infection and aflatoxin B1 exposure.

机构信息

Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Guangxi Cancer Institute, Hospital Oncology School, Guangxi Cancer Center, Nanning, 530021, China.

Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, 530021, China.

出版信息

Cancer Med. 2017 Oct;6(10):2357-2369. doi: 10.1002/cam4.1176. Epub 2017 Sep 21.

Abstract

This study aims to clarify the relationship and mechanism between expression of autophagy-related protein P62 and prognosis of patients with hepatocellular carcinoma (HCC) involving chronic hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure. HCC patients who underwent resection were divided into three groups: HBV(+)/AFB1(+) (n = 26), HBV(+)/AFB1(-) (n = 68), and HBV(-)/AFB1(-) (n = 14). The groups were compared in terms of mRNA and protein levels of P62, disease-free survival (DFS), and overall survival (OS) and the expression of NRF2, Nqo1, and AKR7A3 in P62 high-expression and low-expression group. HBV(+)/AFB1(+) group has lower DFS and OS, and higher P62 expression than in the other two groups. P62 expression generally correlated with elevated NRF2 and Nqo1 expression, and reduced AKR7A3 expression. Patients expressing high levels of P62 showed significantly lower DFS and OS rates than patients expressing low levels. HCC involving HBV infection and AFB1 exposure is associated with relatively high risk of tumor recurrence, and this poor prognosis may relate to high P62 expression. High P62 expression activates the NRF2 pathway, promotes tumor recurrence. The downregulation of AKR7A3 also reduced liver detoxification of aflatoxin B1.

摘要

本研究旨在阐明自噬相关蛋白 P62 的表达与慢性乙型肝炎病毒(HBV)感染和黄曲霉毒素 B1(AFB1)暴露相关肝细胞癌(HCC)患者预后的关系和机制。对接受切除术的 HCC 患者进行分组:HBV(+)/AFB1(+)(n=26)、HBV(+)/AFB1(-)(n=68)和 HBV(-)/AFB1(-)(n=14)。比较三组 P62 的 mRNA 和蛋白水平、无病生存期(DFS)、总生存期(OS)和 P62 高表达和低表达组中 NRF2、Nqo1 和 AKR7A3 的表达。HBV(+)/AFB1(+)组的 DFS 和 OS 较低,P62 表达高于其他两组。P62 表达通常与 NRF2 和 Nqo1 表达升高以及 AKR7A3 表达降低相关。P62 高表达的患者 DFS 和 OS 率明显低于 P62 低表达的患者。HBV 感染和 AFB1 暴露相关的 HCC 与肿瘤复发的相对高风险相关,这种不良预后可能与 P62 高表达有关。高 P62 表达激活了 NRF2 通路,促进了肿瘤复发。AKR7A3 的下调也降低了肝脏对黄曲霉毒素 B1 的解毒作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2247/5633547/5219e6457ee4/CAM4-6-2357-g001.jpg

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