The Correlation Between SLC30A10,SOD2 And The Efficacy Of Sorafenib In Advanced Hepatocellular Carcinoma

Objectives The relationship between the expression of proteins that regulate the trace element manganese in liver cancer cells and the efficacy of sorafenib treatment is poorly understood.To investigate the expression of solute carrier family 30 member 10(SLC30A10)protein that regulates intracellular manganese content and superoxide dismutase 2(SOD2),an essential component of manganese as an active center,in hepatocellular carcinoma cells.To analyze the relationship between SLC30A10,SOD2 and the clinicopathological characteristics of hepatocellular carcinoma and efficacy of sorafenib treatment.Methods The pathological specimens and clinical data of 45 patients with hepatocellular carcinoma recurrence or metastasis after radical resection and undergoing sorafenib treatment were collected.Immunohistochemistry(IHC)was used to detect the expression of SLC30A10 and SOD2 protein in hepatocellular carcinoma tissues and their adjacent tissues.SPSS22.0 software was used to process the data.The adoption rate was used to represent the count data.The chi-squareBtest was used to analyze the differences between the groups.The Spearman rank sum test was used to analyze the correlation.The univariate analysis was performed using The Kaplan-Meier method and the log-rank test.The multivariate analysis was performed using the COX risk regression model.P<0.2 was statistically significant for Univariate analysis,while other P<0.05 was considered statistically significant.Results 1.SLC30A10 was mainly located in the cytoplasm,the positive expression rate in cancer tissues was 51.1%,and the positive rate of paracancerous tissues was 40%(P=0.29).The expression of SLC30A10 in cancer tissue was not associated with preoperative gender,age,AFP,history of liver cirrhosis,tumor diameter,tumor number,BCLC stages,degree of differentiation,vascular tumor emboli and capsule invasion(all P>0.05).2.SOD2 was mainly located in cytoplasm and cell membrane.The positive expression rate of cancer tissue was 62.2%,the positive rate of paracancerous tissues was 86.7%(P=0.008).The expression of SOD2 in cancer tissue was correlated with tumor capsule invasion(P=0.008).3.The median RFS was 4.10 months(95% CI: 3.18-5.02)in all patients.The median postoperative RFS was 4.10 months in patients with SLC30A10 positive expression in cancer tissue,and 3.93 months in the negative group,there was no significant difference between the two groups(P=0.778).The median postoperative RFS in the paracancerous tissues with SLC30A10 negative expression was 5.07 months,which was longer than the 3.23 months in the positive group(P=0.031).Median RFS for SLC30A10 cancer/adjacent(+/-)patients was 5.07 months,which was significantly longer than cancer/cancer adjacent(-/+)patients(3.2 months)(P=0.016).COX risk regression model analysis showed that SLC30A10 cancer/cancer(+/-)was not an independent factor that affected postoperative RFS in patients with HCC(P=0.076).The median RFS in cancer tissue with SOD2 positive expression was 5.0 months,and the negative group was 3.83 months.(P = 0.15).There was no correlation between SOD2 cancer/paracancerous expression and postoperative RFS(P>0.05).Four groups were divided according to cancer tissue SLC30A10/SOD2 expression,survival analysis showed that the median RFS of the SLC30A10/SOD2(-/+)group was 5.0 months and(+/+)was 3.23 months,which were all longer than that of the(-/-)group of 1.97 months(P=0.014,P=0.048).COX regression analysis showed that SLC30A10/SOD2(-/+)was an independent factor affecting postoperative RFS in HCC patients(P=0.027).SLC30A10/SOD2(+/+)was not an independent factor that influences postoperative RFS in patients with HCC(P=0.076).4.The median PFS for Sorafenib treatment in the whole group was 7.17 months(95% CI: 4.41 to 9.93),and the median OS was 20.7 months(95% CI: 13.182 to 28.218).Median PFS and median OS were 7.2 months and 24.37 months in patients with positive expression of SLC30A10 in cancer tissues,and 6.5 months and 18.53 months in patients with negative expressions,respectively,with no statistically significant difference(P>0.05).COX regression model analysis showed that the expression of SLC30A10 in cancer tissues was not an independent factor in the survival time of sorafenib treatment in advanced hepatocellular carcinoma patients(P>0.05).The median OS of SOD2 positive expression in cancer tissues was 24.27 months,and the negative group was 14.06 months.(P=0.043).The median PFS of SOD2 positive and negative patients in cancer tissues were 8.13 months and 6.03 months,respectively,and the difference was not statistically significant(P>0.05).COX regression analysis showed that the expression of SOD2 in cancer tissue was an independent factor of overall survival after sorafenib treatment in patients with advanced HCC.According to the expression of SLC30A10 and SOD2 in HCC patients,the median OS of SLC30A10/SOD2(+/+)group was 32.3 months,which was significantly longer than 14.06 months in the SLC30A10/SOD2(+/-)group(P=0.006)and 12.07 months in the SLC30A10/SOD2(-/-)group(P=0.137).COX regression analysis showed that SLC30A10/SOD2(+/+)expression was an independent factor in the sorafenib treatment of OS in patients with advanced HCC.Conculsions 1.The expression of SLC30A10 between cancer tissues and adjacent tissues was no significant difference in patients with hepatocellular carcinoma.2.The expression of SOD2 was significantly lower in cancer tissue than in adjacent tissues of hepatocellular carcinoma patients.The expression of SOD2 was related to whether the tumor capsule was invaded.The negative expression of SOD2 was more common in the tumor envelope.3.The expression of SLC30A10 may be a potential predictor of prognosis of HCC,the expression of SOD2 may be an independent factor in the treatment of OS in advanced HCC patients with sorafenib,which deserves further study.