Alpha-fetoprotein Combined With Beta2 Adrenergic Receptor Test To Improve The Prognostic Value Of Patients With Hepatocellular Carcinoma After Hepatectomy

Objective: Hepatocellular Carcinoma(HCC) is one of common malignant tumors of the digestive system, and it’s annual mortality ranked the third in C hina. C urrently the main treatment method is hepatectomy, whereas patients have a high rate of recurrence and metastasis, as well as poor prognosis. There have been a lot of research about Beta2 Adrenergic Receptor(β2-AR) and Alpha- fetoprotein(AFP) in HCC prognosis, but the conclusions are not entirely consistent, and there is no study combining with them to evaluate the prognosis on patients with HCC undergoing surgical resection. The aim of this research is to study the expression of β2-AR in HCC, observe the correlation between β2-AR and AFP, examine the association of them with those clinic pathological features respectively, and explore the evaluated ability of patients’ prognosis by AFP combined β2-AR.Methods: 147 HCC patients underwent surgical resection from January 2001 to December 2013 in first affiliated hospital of Dalian Medical University were enrolled retrospectively. They all met the Criteria for diagnosis and treatment of primary liver cancer(2011), and the biopsy pathology of their liver is HCC.We performed on a tissue microarray of 147 HCC tumor samples and test value of serum AFP, then collected corresponding clinical data and survival from Medical records/Centers for Disease Control. Apply χ2test to analyze relationship between clinic pathological features, β2-AR and AFP. Survival predictors were identified by Kaplan-Meier method and Cox proportional hazards regression. Log-Rank test was used for comparison of two or more sets of survival curves. The area under the receiver operating curve(ROC)(AUC) was calculated to evaluate the prognostic ability of survival by AFP and β2-AR.Result1. Analysis of HCC patients’ clinical featuresClinical features are divided into the following four areas: general information(gender, age); HCC pathological features(degree of differentiation, TNM stage, BLAC stage, number of tumors, tumor size); serology including tumor markers(AFP), liver function(ALT, Child-Pugh classification, INR), and blood test(platelets); moreover, the history of hepatitis virus infection.2. Expression of β2-AR in HCCAmong the 147 cases of HCC, the expressions of β2-AR in 110 cases are positive, 37 cases are negative, and the positive rate of β2-AR was up to 74.8%.3. Correlation with AFP stratification and β2-AR proteinRespectively, the expression of β2-AR protein and AFP stratification had a significant difference(χ2 = 9.321, p=0.002), and there was a positive correlation between them(R = 0.256, p = 0.002).4. Relation between β2-AR、AFP stratification and clinical featuresStatistical analysis showed an obvious correlation between β2-AR expression AFP, and TNM stage(p <0.05). The AFP stratification(400ug/L or less and >400ug/L) was related to gender, age, tumor size, and TNM stage(p <0.05), suggesting both of them were closely associated with tumor progression.5. Univariate analysis of prognosis on HCC patients with β2-AR and AFP stratificationThe analysis showed statistically obvious difference between negative and positive expression of β2-AR in overall survival(OS) by Kaplan-Meier method(p = 0.002, p <0.05), and the positive group has a shorter OS. The OS of patients with AFP> 400 ug / L compared with AFP≤400ug / L was significantly decreased(p = 0.015, p <0.05); BLAC stage, Child grade, TNM stage, and PLT stratification were also statistically significant(p <0.05) on the prognosis of patients(p <0.05). stratification6. Multivariate analysis of prognosis on HCC patients with β2-AR and AFPThe result showed that the expression of β2-AR protein, BLAC stage, C hild-Pugh classification, and PLT stratification were the main independent risk factor predicting the prognosis of HCC patients via multivariate analysis of COX proportional hazards regression model(p<0.05), whereas TNM stage and AFP level impacting on overall survival were not independent predictors(p>0.05).7. Analysis of β2-AR and AFP with the prognosis on HCC patientsThe results by Kaplan-Meier method indicated that β2-AR(+)+AFP(+) group compared with β2-AR(+)+AFP(-) group had a poor prognosis; the latter one was poor than β2-AR(-)+AFP(-) group on prognosis.8. The ability of β2-AR, AFP stratification and combination of them to assess overall survivalThe viability assessment on 1,3-year survival rate after resection in patients with HCC as follows. The area under the ROC curve of β2-AR, AFP and β2-AR+AFP 0.642, 0.631 and 0.716 respectively. And that 3 years after resection were 0.615, 0.574 and 0.650.In general the area under the ROC curve :(β2-AR+AFP)>β2-AR>AFP, indicating better judgment on the prognosis with both index.Conclusion1. Serum Alpha-fetoprotein can assess the prognosis of hepatocellular carcinoma patients after radical resection at a certain level.2. Beta2 adrenergic receptor, BLAC stage, C hild-Pugh classification, and PLT stratification are independent risk factors to predict the prognosis of hepatocellular carcinoma patients.3. Combined serum Alpha-fetoprotein with beta2 adrenergic receptor in organization can better judge the prognosis of patients with hepatocellular carcinoma.