Differential expression of Rab27A/B correlates with clinical outcome in hepatocellular carcinoma

AIM:To investigate the association of Rab27A and Rab27B expression with clinicopathological characteristics and prognosis of hepatocellular carcinoma(HCC).METHODS:We used reverse transcription polymerase chain reaction(RT-PCR),real-time PCR,and Western blotting to detect Rab27A and Rab27B mRNA and protein expression in 5 human HCC lines and the immortalized hepatic HL-7702 cell line.We further examined 148 primary HCC samples matched with adjacent normal tissue and 80 non-HCC specimens by immunohistochemistry to evaluate the correlation of Rab27A and Rab27B expression with clinicopathological features and prognosis.RESULTS:Our data showed that Rab27A and Rab27Bwere differentially expressed in cell lines and primary HCC tumors.Rab27A mRNA and protein were detected in 67%(4/6)of human cell lines and 80%(4/5)of HCC cell lines,while Rab27B was found in 50%(3/6)of human lines and 40%(2/5)of HCC lines.Rab27A expression was higher in primary HCC(46.2%,66/143)than in matched adjacent tissue(24.3%,33/136,P<0.001),whereas immunopositivity for Rab27B was lower in primary HCC(57.4%,81/141)than in matched adjacent tissue(87.5%,119/136,P<0.001).Analysis of clinicopathological characteristics of 148 HCC specimens revealed significant correlations between Rab27A and Rab27B expression and tumor tumor-node-metastasis(TNM)classification(P=0.046 and P=0.027,respectively),and between strong Rab27A expression and tumor differentiation grade(P=0.008).Survival analyses revealed that patients with Rab27A+or Rab27B+tumors had significantly reduced overall survival compared with that of patients with Rab27A-or Rab27B-tumors(P= 0.015 and P=0.005,respectively).Risk analyses revealed that Rab27B+and TNMⅢ-Ⅳwere independent poor prognosis factors associated with a 3.36-and 3.37fold higher relative risk of death,respectively.CONCLUSION:Rab27A and Rab27B expression were closely correlated with tumor progression and can be valuable prognostic indicators for HCC patients.