Expression And Clinical Significance Of HIF-1α,SLC30A10,SOD2,PHD2 In Patients With Hepatocellular Cancer

Purpose:At present,the relationship between the regulation of trace elements in cancer cells and the hypoxic pathway is still unknown.This study aims to explore the key regulatory protein HIF-1α(hypoxia-inducible factor-1α),the protein SLC30A10(solute carrier family member 30)10 that regulates manganese content in liver cancer patients,and the manganese element as the essential active center The expression of SOD2(superoxide dismutase 2)and hypoxia response element PHD2(proline hydroxylase 2)regulated by oxygen concentration and its relationship with clinicopathological characteristics,and to find potential therapeutic targets.Method:A total of 76 healthy medical examinees and 105 patients with primary liver cancer who were first diagnosed with serum samples were collected and their clinicopathological data.Among them,75 of them underwent surgical treatment of liver cancer.ELISA was used to measure the expression of HIF-1a in the serum of healthy people and patients with hepatocellular carcinoma,and IHC was used to Detect of HIF-1α,SLC30A10,SOD2,PHD2 Expression in Hepatocellular Carcinoma tissues.SPSS 22.0 software was used for data analysis to compare the difference of serum HIF-1αexpression between groups and the consistency of HIF-1αexpression in HCC serum and tissues.The relationship between the expression of HIF-1α,SLC30A10,SOD2 and PHD2 in HCC cancer tissues and clinicopathology and the correlation between the four proteins were compared.Result:1.The expression level of serum HIF-1αin patients with liver cancer is significantly higher than that of healthy medical examiners(1643.88±777.82 VS793.77±393.86,P=0.0002).2.In patients with liver cancer,serum HIF-1αlevel was associated with AFP level,tumor diameter,tumor number,liver cirrhosis,Child-Pugh classification,vascular invasion,capsule invasion and BCLC stage(P<0.05),and was related to age,gender,HBs Ag,Edmondson-Steiner classification was not related to vascular cancer thrombus(P>0.05);further partial correlation analysis was used to control confounding factors and showed that serum HIF-1αlevel was positively correlated with BCLC stage(r=0.527,P=0.000).3.The positive expression of HIF-1αcan be seen in the nucleus and cytoplasm of liver cancer cells,and the positive expression rate in HCC cancer tissues is 53.3%(40/75).The expression of HIF-1αwas related to AFP,tumor number,tumor capsule invasion,vascular tumor thrombus and BCLC stage(χ~2=6.602,P=0.010;χ~2=5.144,P=0.023;χ~2=4.945,P=0.026;χ~2=4.209,P=0.040;χ~2=30.685,P=0.000,respectively).After using partial correlation analysis to control confounding factors,HIF-1αexpression was positively correlated with BCLC stage(r=0.392,P=0.001).4.The expression of HIF-1αin serum of HCC patients was positively correlated with cancer tissues(r=0.467,P=0.000).5.The positive expression of SLC30A10 was mainly found in the hepatocellular carcinoma plasma,and the positive expression rate in HCC cancer tissue was 72.0%(54/75).The expression of SLC30A10 was related to tumor capsule invasion and vascular tumor thrombus(c~2=8.250,P=0.004;c~2=6.031,P=0.014,respectively);the use of partial correlation analysis to control confounding factors showed that the expression of SLC30A10 was related to the tumor package Membrane invasion was positively correlated(r=0.330,P=0.008).6.The positive expression of SOD2 is mainly seen in the liver cancer cell plasma,and the positive expression rate in HCC cancer tissues is 37.3%(28/75).SOD2 expression was related to Edmondson-Steiner grade and tumor number(c~2=14.079,P=0.000;c~2=5.989,P=0.014,respectively);using partial correlation analysis to control confounding factors showed that SOD2 expression was related to Edmondson-Steiner grade It was negatively correlated(r=-0.404,P=0.001)and positively correlated with the number of tumors(r=0.328,P=0.009).7.The positive expression of PHD2 is mainly seen in the plasma of liver cancer cells,and the positive expression rate in HCC cancer tissues reaches 21.3%(16/75).The expression of PHD2 was related to tumor capsule invasion and vascular cancer thrombus(c~2=5.562,P=0.018;c~2=4.041,P=0.044);the use of partial correlation analysis to control confounding factors showed that the expression of PHD2 was related to the tumor envelope Membrane invasion was positively correlated(r=0.330,P=0.008).8.According to correlation analysis,HIF-1αand PHD2 were positively correlated in HCC cancer tissues(r=0.331,P=0.000),PHD2 and SOD2 were negatively correlated in HCC cancer tissues(r=-0.176,P=0.031),SOD2 and SLC30A10 were negatively correlated in HCC cancer tissues(r=-0.348,P=0.000).Conclusion:1.HIF-1αis significantly increased in the serum of liver cancer patients,and it is positively correlated with its expression in liver cancer tissues,both of which are positively correlated with the BCLC stage of liver cancer,suggesting that the detection of serum HIF-1αlevel helps to determine the stage of liver cancer.2.In HCC cancer tissues,the expressions of HIF-1α、SLC30A10,SOD2 and PHD2 are correlated with tumor number,envelope invasion,and BCLC stage,suggesting that they may be involved in malignant biological behaviors such as HCC generation,invasion,and infiltration.3.In HCC cancer tissues,the expressions of HIF-1α、SLC30A10,SOD2 and PHD2 are related to each other,and in-depth study of their internal pathway mechanisms can help to find potential therapeutic targets.