The Relationship Analysis Between FXR And Regulated Genes Expression And Clinical Prognosis In Patients With Primary Liver Cancer

Objective:To identify factors predictive of survival for primary liver cancer is important for disease evaluation and treatment. The nuclear receptor FXR has been confirmed as a repressor of liver tumor. In this study, we aim to investigate the prognostic values of the FXR and its regulated genes, the serum markers and the individual tumor characteristic in predicting survival.Methods:The tumor tissues from 26 cases of patients with primary liver cancer which were treated with surgery alone were collected for the detection of the expression of FXR, MDR3, and MRP by fluorescence quantitative real time PCR. Other information of the patients like the characteristics of the tumor, the preoperative and postoperative serum markers (AFP, TB, CB, TBA) were collected from our hospital system. Every patient's survival information was collected by telephone visits, Survival curves were calculated by Kaplan-Meier method and compared by the log-rank test, Breslow test and T-W test. Cox proportional hazards models were used for multivariate analysis to explore the independent prognostic factors, and a P-value<0.05 was considered significant. Furthermore, according to invasive ability and the level of gene expression, stratified subgroup survival analysis for 26 patients was also carried out.Results:The overall 1-,2-and 5-year survival rates for the primary liver cancer patients in this study were 58%,38% and 7%. The group showing high expression of FXR had a significantly longer median overall survival than the group showing low expression of FXR (26.80 months VS 7.27 months, p<0.05). The overall 1-and 2-year survival rates for the group showing high expression of FXR were 77% and 53%. and that for the group showing low expression of FXR were 38% and 23%. The group showing increased TB after operation had a significantly longer median overall survival than the group showing reduced TB after operation (10.73 months VS 27.27 months, p<0.05). For the patients with hepatocellular carcinoma, the group showing high expression of FXR had a significantly longer median overall survival than the group showing low expression of FXR (26.80 months VS 6.97 months, p<0.05). The group showing high expression of FXR and low invasive-ability had a remarkably longer median overall survival than the other three group (27.27 months, p<0.05). Cox regression revealed the FXR and TBA were independent factors for survival in the primary liver cancer patients (p<0.05). Cox regression also indicated the FXR and MRP were independent factors for survival in the hepatocellular carcinoma patients (p<0.05).Conclusion:Our data suggested that FXR might function as a tumor suppressor gene for primary liver cancer and be a candidate biomarker for predicting survival of primary liver cancer, especially when combining with tumor invasive-ability. Other factors, such as reduced expression of TB after operation and low invasive-ability. might facilitate to predict survival of patients with primary liver cancer.