Expression Of Receptor For Hyaluronan-Mediated Motility In Patients With Hepatocellular Carcinoma

Objective: In order to assess the correlation between the expression of RHAMM(Receptor for hyaluronic acid(HA)- mediated motility) m RNA and clinicopathologic datas in HCC(Hepatocellular carcinoma, HCC) patients, we detected the levels of RHAMM m RNA expression in human HCCs and their ANLTs(adjacent normal liver tissues, ANLT). So that, we could find out the prognostic significance of RHAMM expression in patients with HCC.Methods : 187 cases of HCC cancer patients who underwent surgical resection at Affiliated Hospital of Guilin Medical University from November 2001 to April 2007 were enrolled in the present study. In addition, ten specimens of normal liver tissues near the hepatic hemangioma tissues were also collected. We examined the RHAMM expression in 187 HCC patients and 10 normal liver tissues by RT-PCR. To further confirm the overexpression of RHAMM at protein level and it’s location in cells, we performed immunohistochemical experiment on 25 pairs of HCC and corresponding 5 ANLTs, and 10 normal liver tissues. And western-blot exprement on 32 pairs of HCC and corresponding ANLTs and 10 normal liver tissues. The statistical analyses were performed using SPSS 13.0 software. Survival curves were generated using the Kaplan-Meier method and checked for statistical significance with the log-rank test. Qualitative variables were compared with the Pearson’s Chi-Square(χ2) test, and the quantitative variables were analyzed by the independent t test. Chi-Square Test was used for correlation analysis. The statistical significance of the differences between mean values was defined as p < 0.05.Results:(1) RHAMM expression was up-regulated in 123 cases(65.8%) of the 187 HCC patients, while down-regulated in 64(34.2%) cases of them(p < 0.001). The results of mmunohistochemical experiment showed that RHAMM was overexpressed in 18(72%) of the 25 HCC tissues compared with their ANLT(p = 0.023), while RHAMM was overexpressed in only 10(40%) of the 25 ANLTs. The results of western-blot showed that RHAMM was overexpressed in 24(75%) of the 32 HCC tissues compared with their ANLT(p = 0.031).(2) The up-regulation of RHAMM is associated with TNM stage, vascular invasion and recurrence in HCC. RHAMM expression was significantly higher in HCC patients with TNM stage(III-IV) than in those with TNM stage(I-II)(χ2 = 5.476, p = 0.019). Moreover, RHAMM expression was also much higher in HCC patients with the presence of vascular invasion(χ2 = 5.327, p = 0.021) and recurrence(χ2 = 4.578, p = 0.032) compared with in those without the presence of vascular invasion and recurrence. However, there was no significant association between the RHAMM m RNA expression and age(≥ 55 years or < 55 years), gender, family history, HBs Ag, level of AFP(≥ 20 ng/m Lor < 20 ng/m L), tumor median size(≥ 5 cm or < 5 cm) and number, winedrinking history, the presence of combined liver cirrhosis, distant metastasis, and LNM(all p > 0.05, Table 1).(3) High RHAMM m RNA expression, tumor size ≥ 5 cm, multiple tumor number, III–IV of TNM stage, and the presence of vascular invasion(p < 0.01) were associated with the shorter disease-free survival and overall survival.(4) High RHAMM expression(HR, 1.574; 95% CI, 1.025-2.419; p = 0.038), tumor size ≥ 5 cm(HR, 1.964; 95% CI, 1.188-3.247; p = 0.008), III–IV of TNM stage(HR, 1.865; 95% CI, 1.157-3.007; p = 0.011) were independent predictors for disease-free survival. High RHAMM expression(HR, 1.739; 95% CI, 1.129-2.680; p = 0.012), tumor size ≥ 5 cm(HR, 1.738; 95% CI, 1.054-2.867; p = 0.030), III–IV of TNM stage(HR, 1.775; 95% CI, 1.109-2.843; p = 0.017), the presence of vascular invasion(HR, 1.599; 95% CI, 1.053-2.427; p = 0.027), and recurrence(HR, 1.739; 95% CI, 1.129-2.680; p < 0.001) were independent predictors for overall survival.Conclusions:(1) High expression of RHAMM was associated with TNM stage, vascular invasion, and recurrence in patients with HCC.(2) High RHAMM expression predicted poor prognosis of HCC by analyzing the relationship between expression of RHAMM and disease-free/overall survival of HCC patients after surgical resections.(3) Our results revealed important role of RHAMM for HCC progress and prognosis, and it may be regarded as a promising therapeutic target for HCC.