Low CADM2 expression predicts high recurrence risk of hepatocellular carcinoma patients after hepatectomy.

To investigate the expression and clinical significance of CADM2 in hepatocellular carcinomas (HCC). The level of expression of CADM2 mRNA was assessed in frozen tumor specimens and adjacent noncancerous tissues from 30 HCC patients by real-time PCR. The protein level was determined by immunohistochemistry on a tissue microarray containing tumor and adjacent noncancerous tissues from 234 HCC patients. Clinicopathological characteristics associated analysis was performed through SPSS18 . CADM2 was strikingly down regulated in HCC. CADM2 expression was associated with differentiation (P = 0.000), serum alpha-fetoprotein (P = 0.003), vascular invasion (P = 0.001), and hepatitis B surface antigen (HBsAg, P = 0.038). Furthermore, patients with low CADM2 expression had significantly poorer recurrence-free survival (RFS) (40.8 and 34.2 % vs. 56.3 and 50.1 % in 3- and 5-year RFS, respectively, P = 0.005). Subgroup analysis revealed that the difference in RFS between groups with low- and high-CADM2 expression still existed among patients belonging to stage 0 or A of BCLC staging system (P = 0.008), patients with tumor ≤5 cm in size (P = 0.013), and alpha-fetoprotein-negative patients (P = 0.003). Moreover, low expression was more frequently observed in the early recurrence group (within 2 years, P = 0.007). Further multivariate Cox regression analysis indicated that CADM2 expression level, tumor size, tumor number, vascular invasion, HBsAg were independent risk factors for HCC recurrence. CADM2 serves as a novel predictor of RFS in HCC patients after curative resection.