Abstract
Objective
To detect expression and phosphorylation level of macrophage migration inhibitor (MIF) and extracellular-regulated kinases 1 and 2 (ERK1/2) in hepatitis B-induced liver cirrhosis (HBILC) and hepatocellular carcinoma (HCC) with a background of HBILC and analyze the correlation of MIF and ERK1/2 with HBILC and HCC.
Methods
Twenty cases of normal liver tissues were collected as a control group, and 48 specimens of HBILC tissues and 48 specimens of HCC tissues were collected as the experimental group, which were assigned as the HBILC group and HCC group, respectively. All tissue specimens were processed into tissue chips. The expressions of MIF, ERK1/2, and their phosphorylated proteins were detected via immunohistochemistry, and MIF and ERK1/2 nucleic acid expressions were detected by in situ hybridization. The results were statistically analyzed using the chi-square test.
Results
Proteins and nucleic acids of MIF and ERK1/2 presented low expression in the control group and high expression in the HBILC group and HCC group. MIF expression in the three groups was 25.0%, 75.0%, and 79.17%, respectively, while that of the nucleic acids was 25.0%, 70.83%, and 68.75%, respectively. Expression of ERK1/2 in the three groups was 40.0%, 60.42%, and 81.25%, respectively, and that of nucleic acids was 40.0%, 79.17%, and 77.08%. Expression of pERK1/2 was low in the control and HBILC group and high in the HCC group. Expression of pERK1/2 in the three groups was 20%, 45.83%, and 75%, respectively. Expression of pERK1/2 in the HCC group was significantly different from that in the HBILC and control group (P<0.05), but the difference between the HBILC group and control group was not statistically significant (P>0.05).
Conclusion
Occurrence and development of HBILC and HCC are not only related to the high expression of MIF but also closely related to the activation of the ERK1/2 signaling pathway.
Data Sharing Statement
The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.
Ethics Approval and Consent to Participate
This study was conducted with approval from the Ethics Committee of the 940 Hospital of Joint Logistic Support Force of People’s Liberation Army. This study was conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from all participants.
Acknowledgment
As one of the members of this study group, some of the pathological specimens involved in Yu Haipeng’s study30 were sourced from the 940th Hospital of the Joint Logistics Support Force of Chinese People’s Liberation Army (normal liver tissues, hepatocellular carcinoma tissues and paracancerous tissues), and the others came from the Cancer Hospital affiliated to Tianjin Medical University Cancer Institute & Hospital (normal liver tissues, hepatocellular carcinoma tissues and paracancerous tissues). In his study, he first detected the expression of MIF, ERK1/2 and p-ERK1/2 in normal liver tissues, hepatocellular carcinoma and paracancerous tissues, as well as the expression of MIFmRNA and ERK1/2 mRNA. He found that the expression of these three proteins and two nucleic acids in hepatocellular carcinoma and paracancerous tissues was significantly higher than that in normal liver tissues, and then focused on adding the recombinant gene MIF (rMIF) to liver cancer cells and normal liver cells. He used Western and RT-PCR methods to detect the expression of ERK1/2, p-ERK1/2 and ERK1/2 mRNA in these two cells. The results showed that with the increase of rMIF concentration, the expression of ERK1/2, p-ERK1/2 and ERK1/2 mRNA was significantly higher than that of normal hepatocytes. The conclusion, MIF may promote the occurrence and development of hepatocellular carcinoma through ERK1/2 signal pathway.
Dr Xiao-Hui Yu is also a member of this subject, and the pathological samples involved in the study were all sourced from the 940th Hospital of the Joint Logistics Support Force of Chinese People’s Liberation Army (normal liver tissues, liver cirrhosis tissues and hepatocellular carcinoma tissues). The study mainly focuses on detecting the expression of three proteins (MIF, ERK1/2 and p-ERK1/2) and two nucleic acids (MIF mRNA and ERK1/2 mRNA) in normal liver, liver cirrhosis and hepatocellular carcinoma tissues. The results showed that the protein and nucleic acid of MIF and ERK1/2 were low expressed in normal liver group, high expressed in cirrhosis group and HCC group, while pERK1/2 was low expressed in normal liver tissues and cirrhosis group, and high expressed in HCC group. The expression of pERK1/2 in HCC group was significantly different from that in cirrhosis group and normal control group (P < 0.05), the expression of pERK1/2 in the cirrhosis group is not significantly different from the normal expression in the normal liver tissues control group (P > 0.05). Thus, the low expression of pERK1/2 in cirrhosis group of this study is different from the high expression in hepatocellular carcinoma tissues of Yu Haipeng, suggesting that the occurrence and development of cirrhosis and hepatocellular carcinoma are not only related to the high expression of MIF, but also may be related to the activation of ERK1/2, a key protein, especially the carcinogenesis of liver cirrhosis is more closely related to the phosphorylation of ERK1/2. Therefore, the study focused on the relationship between the occurrence of canceration of liver cirrhosis and the phosphorylation of ERK1/2.
Disclosure
The authors report no conflicts of interest in this work.