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

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.

p62/SQSTM1 expression in canine mammary tumours: Evolutionary notes

“…Numerous studies report different p62 expression patterns in different types of human cancers of different origins: the protein is overexpressed in prostate, digestive system, liver and lung carcinoma or down‐regulated in oesophageal adenocarcinomas and colorectal cancers …”

“…To add a further layer of complexity studies mainly focused on human in pancreatic ductal carcinoma suggest that both p62 overexpression in cancer cells and its down regulation in tumour microenvironment promote tumour . In contrast, elevated p62 levels in the stroma seem to induce tumour suppression by intertwined anti‐inflammatory/metabolic responses . Thus, homeostatic maintenance of p62 in both cancer and stroma seems to dictate the final outcome of the tumorigenic process .…”

Modulation of the Autophagy-Lysosomal Pathway in Hepatocellular Carcinoma Using Small Molecules

“…Interestingly, deletion of p62 or NRF2 in mice with liver-specific ATG7 or ATG5 deficiency decreased liver tumor development, implying that the p62-KEAP1-NRF2 axis contributes to tumorigenesis [26,30]. Moreover, p62 accumulation and NRF2 activation were found in HCC patients and were correlated with a poor overall survival rate in HCC caused by HBV and aflatoxin B1 [31,32]. Thus, the p62-KEAP1-NRF2 axis could serve as the key driver of human HCC.…”

CBX4 Expression and AFB1-Related Liver Cancer Prognosis

“…the most important cause for this high AIR and ADR [1]. AFB1 is a known I-type chemical carcinogen produced by Aspergillus parasiticus and Aspergillus flavus, and has been proved to involve in the carcinogenesis and progression of HCC [4][5][6][7][8][9][10]. This carcinogenicity of AFB1 mainly results from its metabolic product binding to DNA and inducing DNA damage.…”

“…These products of AFB1, especially AFBEX, are characterized by high reaction, genic toxicity, and carcinogenicity [3]. Evidence from molecular epidemiology and animal models has shown that AFB1 is an important carcinogen inducing hepatocellular carcinoma (HCC) [4][5][6][7][8][9][10]. Mechanically, the carcinogenesis of AFB1-related HCC mainly involves in the formation of DNA damage (including AFB1-DNA adducts, DNA single-strand breaks, DNA double-strands breaks, and gene mutations), the inactivation of such tumor suppressor gene as TP53, and the activation of cancer genes such as Ras [3,[11][12][13][14][15].…”