The Relationship Between Serum Apolipoprotein B And Postoperative Survival In Patients With Primary Liver Cancer

To date,curative resection remains to be the most optimal therapeutic choice of hepatocellular carcinoma(HCC),though the overall survival(OS)remains extremely unsatisfactory.To manage the HCC patients better,more markers that predict postoperative survival should be explored.As the liver plays an important role in lipid metabolism,the level of lipids are closely related to the change of liver function.So,measuring blood lipid level might be an important factor in evaluating the progression of liver disease.Many apolipoprotein molecules and their derivatives have been shown to be associated with the prognosis of many cancers.Low-density lipoprotein and apolipoprotein A1(ApoAl)have been reported in the literature that they could be used as prognosis predicting markers for HCC patients who underwent curative liver resection.Obj ectiveThis study compared the serum apolipoprotein B(ApoB)levels among patients with different hepatitis B-related liver diseases,and explored the correlation between preoperative serum ApoB levels and postoperative survival in patients with primary liver cancer.Materials and MethodsA total of 3,192 liver patients who met the criteria were enrolled in the study,including 188 HCC patients who had undergone curative liver resection in Henan Cancer Hospital and their follow-up information of 5 years were collected,and 3004 liver patients with infection of hepatitis B virus who were under treatment in the Fifth Medical Center of the People's Liberation Army Hospital.The t-test and one-way ANOVA were used to compare the lipoprotein levels in the serum among patients with different liver diseases.Kaplan-Meier curve and Cox regression models were used to analyze the factors affecting the prognosis of patients with primary liver cancer.The life table method was used to compare the 1-,3-,and 5-year survival rates in patients with primary liver cancer;Correlation and Logistic regression models were used to analyze the relationship between serum ApoB and other clinical variables.Fluorescence quantitative PCR experiments were used to compare the expression of ApoB related genes between matched cancer tissues and adj acent tissues and adj acent tumor tissues with different liver cirrhosis backgrounds.All of the statistical tests were based on a two-sided probability,with a significance level of 0.05,and were performed in SPSS 21.0(Xishu Software Company,Shanghai,China).Results1.The results of One-way ANOVA showed that serum ApoB levels were lower in patients with cirrhosis than in patients with chronic hepatitis B(P<0.001),while serum ApoB levels were elevated in patients with primary liver cancer(P<0.001).Serum ApoAl levels in patients with cirrhosis and primary liver cancer were lower than those in patients with chronic hepatitis B(P<0.001),and serum ApoAl levels in patients with primary liver cancer were higher than those in patients with cirrhosis(P<0.001);2.Through univariate and multivariate cox regression,we found that preoperative serum ApoB level was an independent postoperative predictor for primary liver cancer with hazard ratio as 1.508(P=0.021).And elevated serum ApoB level was associated with worse postsurgery prognosis in primary liver cancer patients(P=0.043)shown by Kaplan-Meier curve.The average survival time of the patients was 20.33 months in the low serum ApoB level group,while the average survival time is only 11.16 months in the high serum ApoB level group.Spearman correlation analysis showed that preoperative serum ApoB levels were associated with tumor size(r=0.300,P<0.001),and the relationship between serum ApoB and low density lipoprotein cholesterol were as high as 0.694(P<0.001);In line with this,further univariate and multivariate logistic regression analysis revealed that patients with higher ApoB in the serum value were more likely to have larger tumor size(?5 cm),with the OR value as high as 7.624(95%CI:1.833-31.715,P=0.005).3.The results of real-time PCR showed that the mRNA expression levels of MTTP and LRP1 in tumor tissues were significantly lower than those in adjacent tissues(P<0.05),the mRNA expression levels of ApoB 100 and LDLR in tumor tissues were slightly lower than those in adjacent tissues,but the difference had no,significance.There was no significant difference in the expression level of ApoB100 and LRP1 mRNA in the presence or absence of cirrhosis,while the expression of LDLR mRNA in the adjacent tumor tissues without background of cirrhosis were higher than that in cirrhosis.(P=0.025).ConclusionApoB could be a valuable novel prognosis predicting marker for HCC patients who underwent curative liver resection.Moreover,elevated ApoB level could indicate worse outcome in HCC patientswhich could be explained by the relationship between ApoB and tumor size.