Differential Expression Of Rab27A/B Correlates With Clinical Outcomes In Gastric, Colorectal Cancer And Hepatocellular Carcinoma

AIM: To investigate the association of Rab27A and Rab27B expression withclinicopathological characteristics and prognosis of hepatocellular carcinoma (HCC).METHODS: We used RT-PCR, real-time PCR, and western blot to detect Rab27A andRab27B mRNA and protein expression in5human HCC lines and the immortalizedhepatic HL-7702cell line. We further examined148primary HCC samples matched withadjacent normal tissue and80non-HCC specimens by immunohistochemistry to evaluatethe correlation of Rab27A and Rab27B expression with clinicopathological features andprognosis.RESULTS: Our data showed that Rab27A and Rab27B were differentially expressed incell lines and primary HCC tumors. Rab27A mRNA and protein were detected in67%(4/6)of human cell lines and80%(4/5) of HCC cell lines, while Rab27B was found in50%(3/6)of human lines and40%(2/5) of HCC lines. Rab27A expression was higher in primaryHCC (46.2%,66/143) than in matched adjacent tissue (24.3%,33/136; P <0.001), whereasimmunopositivity for Rab27B was lower in primary HCC (57.4%,81/141) than in matchedadjacent tissue (87.5%,119/136; P <0.001). Analysis of clinicopathological characteristicsof148HCC specimens revealed significant correlations between Rab27A and Rab27Bexpression and tumor TNM classification (P=0.046and P=0.027, respectively), andbetween strong Rab27A expression and tumor differentiation grade (P=0.008). Survivalanalyses revealed that patients with Rab27A+or Rab27B+tumors had significantly reducedoverall survival compared with that of patients with Rab27A-or Rab27B-tumors (P=0.015and P=0.005, respectively). Moreover, patients with Rab27A-/Rab27B-tumors hadthe longest survival, while those with Rab27A+/Rab27B+tumors had the poorest survival.Risk analyses revealed that Rab27B+and TNM III-IV were independent poor prognosisfactors associated with a3.36-and3.37-fold higher relative risk of death, respectively.CONCLUSION: Rab27A and Rab27B expression were closely correlated with tumorprogression and can be valuable prognostic indicators for HCC patients. Purpose: To analyze the association of Rab27A and Rab27B expression withclinicopathological characteristics of gastric cancer (GC) and colorectal cancer (CRC) andclarify their distinct roles in disease progression.Methods: We used semi-quantitative and quantitative PCR, western blot to detect Rab27Aand Rab27B mRNA and protein expression in13human GC and CRC cell lines. Wefurther examined1316primary tumor samples including910GC and406CRC byimmunohistochemistry assessment to evaluate the relationships of Rab27A and Rab27Bexpression and clinicopathological features in the cohort.Results: Our data showed that Rab27A and Rab27B were differentially expressed in celllines and primary tumors of GC and CRC. Positive expression of Rab27A and Rab27BRNA and protein in the13cell lines was46.2%,38.5%, respectively. Rab27A and Rab27Bexpression was negative or faint in primary GC (28.6%,247/865;28.9%,252/873) andCRC (34%,132/388;30.6%,121/395) tissues compared with adjacent normal gastric(76.6%,160/209, P<0.001;79.5%,167/210, P<0.001) and colorectal (46.6%,76/163,P=0.005;38.3%,62/162, P=0.081) mucosa specimens. Both Rab27A+and Rab27B+wasassociated with well differentiation, negative vascular invasion, TNM I–II and longersurvival etc., whereas Rab27A-and Rab27B-was correlated with poorly differentiation,vascular invasion, TNM III–IV and reduced survival etc. in GC and CRC. Patients withRab27A+/Rab27B+had the longest survival, but Rab27A-/Rab27B-had the poorestsurvival in these cancers. Moreover, Cox proportional hazards model revealedRab27A+/Rab27B+expression was a protective prognosis factor in both GC and CRC, andRab27A-and Rab27B-were independent poor prognosis factors in GC. There was astatistical correlation between the expression of Rab27A and Rab27B in GC and CRC, butfor the clinicopathological features and prognosis, Rab27A seemed to play a key role.Conclusions: Rab27A and Rab27B play a role in the tumour progression and metastasis ofGC and CRC, which could be valuable prognosis indicators for the patients.